Patent Docs

Webinar on AIA and Patent Due Diligence

Strafford will be offering a webinar/teleconference entitled "AIA and Patent Due Diligence Understanding the AIA Impact and Best Practices for the Due Diligence Process" on May 29, 2013 from 1:00 - 2:30 pm (EDT).  Thomas L. Irving of Finnegan Henderson Farabow Garrett & Dunner and Lauren L. Stevens of Global Patent Group will provide guidance to patent counsel regarding the impact of the Leahy-Smith America Invents Act on patent due diligence, and offer best practices for conducting due diligence in light of the AIA.  The panel will review the following questions:

• How do the AIA and recent court decisions affect the due diligence process?
• Is an application correctly filed in the name of the applicant or should it be filed in the name of the inventors because it is under the old 120/119(e)?
• What changes should patent counsel make in the due diligence process as a result of the AIA?

The registration fee for the webinar is $297 ($362 for registration and CLE processing).  Those registering by May 3, 2013 will receive a $50 discount.  Those interested in registering for the webinar, can do so here.

IPO Conference on a Harmonized Patent World

The Intellectual Property Owners Association (IPO) European Practice Committee will be hosting a one-day conference entitled "A Harmonized Patent World -- Are We Getting There?" on May 27, 2013 in Brussels, Belgium.  The conference will analyze harmonized litigation in Europe, including discussions on the Unified Patent Court, The Commission and the Court in Germany, and cover global harmonization and central versus national prosecution including the PCT-PPH route and UK prosecution as an alternative.

A program for the conference, including an agenda and list of speakers can be found here.  There is no registration fee for the conference, but those interested in attending must register and can do so here.

What We May Learn from the Myriad Oral Argument

By Kevin E. Noonan --

The U.S. Supreme Court heard oral argument in Association for Molecular Pathology v. Myriad Genetics, Inc. on Monday, and many have commented on the Court's interrogation of the parties' representatives (and the government) and how those representatives responded to the Justices' questioning.  On balance, it seems fruitless to bemoan the apparent difficulties the Court has with these issues; to paraphrase the sponsor of the aspartame patent term extension (private) bill, "you go to patent law with the Supreme Court you have."  Equally unavailing are discussions of the ACLU's perfidity (in advancing arguments having little resemblance to the law or the facts), the government's duplicity (asserting that genomic DNA should not be patent-eligible after more than thirty years of granting, and continuing to grant, such patents), any perceived incompetence by Myriad's representatives (for being unable to do the near impossible in answering the Court's sometimes incoherent questions) or Myriad's irresponsibility (for continuing a suit on patents that do not protect its core business and putting at risk patents to others necessary for commercialization).

While assessing (or worse, trying to predict) the Court's take on the issue, there are a few aspects that are evident:

Bad analogies make bad law:  Isolated human DNA is not a tree (Justice Kagan); sap from a tree (Justice Breyer); a chocolate chip cookie (Justice Sotomayor); a baseball bat (Greg Castanias); or a liver or kidney (Chris Hanson).  Instead of dancing around the issues by waxing poetic with analogies, the Court might have (and at least Myriad should have given them an opportunity to) considered more realistic comparisons.  For example, it should not too much to ask the Court if any of the following are or should be patent-eligible:

• Isolated chemical compound from crude oil useful as a lubricant
• Isolated chemical compound from a plant useful as a drug
• Isolated antibiotic produced by bacteria
• Isolated protein from an animal useful to cure/ameliorate human disease
• Isolated cucumber gene that extends freshness
• Isolated human gene (erythropoietin)

The Goldilocks view of patent law:  Justice Breyer still believes it is the Court's role to make sure the amount of patenting is just right regarding the balance between too much (retarding innovation) and too little (providing insufficient incentives for commercialization).  And while colorful, colloquies such as the following:

It's important to keep products of nature free of the restrictions that patents there are, so when Captain Ferno goes to the Amazon and discovers 50 new types of plants, saps and medicines, discovers them, although that expedition was expensive, although nobody had found it before, he can't get a patent on the thing itself.  He gets a patent on the process, on the use of the thing, but not the thing itself.

Not only do not answer the question but obscure it.  It is also disquieting to hear that the Justice thinks that the "product of nature" prohibition is "horn-book law"; were that the case, the Court would not need to consider the question before it.

The Court remains cautious regarding its capacity to harm incentives for commercialization:  This concern was expressed by many members of the Court, not limited to those Justices (such as Justices Scalia or Alito) who might be expected to voice these sentiments.  Indeed, Justice Kennedy's questions regarding the effects of a negative decision might indicate that there are sufficient members of the Court who might be persuaded that the more prudent course would be to affirm.

The government's position has the best chance of prevailing:  Not surprisingly, the "compromise" position espoused by the government (that cDNA is patent-eligible, but genomic DNA is not) seemed to have significant traction with the Court, if only because (as it did at the Federal Circuit) the presence of the "hand of man" is most evident for these embodiments of isolated DNA claims.  (The question of whether cDNA is obvious, as discussed by some members of the Court, falls into the category of battles to be fought another day.)  The Court did not fail to appreciate the change in the government's position, with Justice Kagan dismissing the PTO's history of granting patents encompassing genomic DNA because the Office was "patent-happy" (this disparagement, while unfair is not surprising in view of the general drumbeat of a "broken patent system" over the past decade from various interest groups).

Patent-eligibility will depend on how subject matter is claimed:  This isn't new, but may take on renewed significance.  Many members of the Court seemed to think that "method" claims (of using or producing) isolated DNA would be sufficient, ignoring the experience of foreign patent systems that eschewed composition protection for pharmaceuticals, for example in favor of such method claims; these generally did not result in robust commercialization of such pharmaceutical products.  Paradoxically, of course, for isolated DNA, "use" claims may be the most important in the future, as the composition of matter claims to DNA per se will not survive into the next decade by the action of patent term limits to 20 years from filing and the publication of the fruits of the Human Genome Project between 1998-2001.  What may not be as clear (or, more troubling, may become crystal clear) is the fate of claims such as Claim 2 in this sequence:

1.  Penicillin.
2.  An isolated preparation of penicillin having a specific activity of x Units/mg.
3.  A pharmaceutical composition comprising a therapeutically effective amount of penicillin and an acceptable diluent, excipient or carrier.

Claim 1 is not patent-eligible today, as it reads on the molecule as it exists in nature, and Claim 3 should remain eligible regardless of the Court's decision in Myriad.  Whether Claim 2 remains patent-eligible will depend on how narrowly the Court bases its decision (in the event that It reverses any portion of the Federal Circuit's decision below) and the amount of dicta that accompanies such a decision.

Ironically, the ACLU may have provided the best rationale for the Court to render a decision that does not do violence to traditional concepts of patenting molecules found in nature, in the following response to Justice Alito's question:

JUSTICE ALITO: Suppose there is a substance, a -- a chemical, a molecule in the -- the leaf -- the leaves of a plant that grows in the Amazon, and it's discovered that this has tremendous medicinal purposes. Let's say it -- it treats breast cancer.

A new discovery, a new way -- a way is found, previously unknown, to extract that. You make a drug out of that. Your answer is that cannot be patent -- patented; it's not eligible for patenting,

MR. HANSEN: If there is no alteration, if we simply pick the leaf off of the tree and swallow it and it has some additional value, then I think it is not patentable. You might be able to get a method patent on it, you might be able to get a use patent on it, but you can't get a composition patent.

JUSTICE ALITO: But you're making -- you the hypotheticals easier than they're
 intended to be. It's not just the case of taking the leaf off the tree and chewing it.  Let's say if you do that, you'd have to eat the whole forest to get the [] value of this. But it's extracted and -- and reduced to a concentrated form. That's not patent -- that's not eligible?

MR. HANSEN: No, that may well be eligible, because you have now taken what was in nature and you've transformed it in two ways. First of all, you've made it substantially more concentrated than it was in nature; and second, you've given it a function. If it doesn't work in the diluted form but does work in a concentrated form, you've given it a new function. And the -- by both changing its nature and by giving it a new function, you may well have patent -­

JUSTICE ALITO: Well, when you concede that, then I'm not sure how you distinguish the isolated DNA here, because it has a different function.

Finally, the fate of claims to oligonucleotide claims is uncertain, although these claims raise other issues of patentability (not patent-eligibility) that may render them invalid if ever asserted against an accuse infringer.

The Court's decision is expected by the end of this term, some time in June.

Biogen Idec, Inc. v. GlaxoSmithKline LLC (Fed. Cir. 2013)

By Donald Zuhn --

Yesterday, in Biogen Idec, Inc. v. GlaxoSmithKline LLC, the Federal Circuit affirmed the determination by the District Court for the Southern District of California that the claim term "anti-CD20 antibody" as used in U.S. Patent No. 7,682,612 was limited by prosecution history estoppel.  The '612 patent is directed to the treatment of hematologic malignancies associated with circulating tumor cells using anti-CD20 antibodies.  Representative claim 1 recites:

1.  A method of treating chronic lymphocytic leukemia in a human patient, comprising administering an anti-CD20 antibody to the patient in an amount effective to treat the chronic lymphocytic leukemia, wherein the method does not include treatment with a radiolabeled anti-CD20 antibody.

As the majority opinion notes, it was initially believed that only one large loop (epitope) of the CD20 antigen (at right) was exposed on the surface of cancerous B cells, and therefore, that there was only one suitable target for the anti-CD20 antibody.  However, after Biogen filed the application that issued as the '612 patent, other researchers discovered that the CD20 antigen had a second small loop to which certain anti-CD20 antibodies could bind.

During the prosecution of the application that issued as the '612 patent, the examiner rejected the claims because the specification did not provide enablement commensurate with the scope of the claimed invention, which the examiner contended included "any and all anti-CD20 antibodies, no matter the specificity or affinity for the specific epitope on the circulating tumor cells."  The examiner acknowledged that the specification was enabling for Biogen's chimeric gamma 1 anti-human CD20 antibody, Rituxan® (rituximab), but was silent concerning the specificity and affinity that would be necessary for other anti-CD20 antibodies.  In response to the rejection, Biogen stated that:

[E]ven though antibodies directed to the same antigen might have different affinities and functional characteristics, one of skill in the art could readily identify an antibody that binds to CD20 with similar affinity and specificity as does RITUXAN® using techniques that are well known in the art.  . . .  With that knowledge in hand, the skilled artisan could readily produce anti-CD20 antibodies using similar techniques, and screen such antibodies for those having an affinity and functional activity similar to RITUXAN®.

The examiner then withdrew the rejection and allowed the application.

In March 2010, Biogen filed suit against GlaxoSmithKline, asserting that GSK's anti-CD20 antibody Arzerra® (ofatumumab) infringed claims 1-4, 6, 8-10, 14-17, 20-22, and 58-60 of the '612 patent.  In contrast with Rituxan®, Arzerra® binds to the second small loop of the CD20 antigen, has a much greater affinity for the CD20 antigen, and is a fully human antibody.  The District Court conducted a Markman hearing to construe three terms, including the term "anti-CD20 antibody."  The District Court rejected Biogen's broad construction of "an antibody that binds to a cell surface CD20 antigen," and instead adopted GSK's construction "rituximab and antibodies that bind to the same epitope of the CD20 antigen with similar affinity and specificity as rituximab."  In adopting the latter construction, the District Court noted that prosecution history disclaimer applied because Biogen had limited the term to overcome the examiner's enablement rejection.  Following this construction, Biogen stipulated to noninfringement and appealed the District Court's construction to the Federal Circuit.

Writing for the majority, Judge Reyna notes that because neither the claims nor the specification compelled a construction that was contrary to the one offered by Biogen, the question before the Court was whether statements in the prosecution history were sufficient to overcome the heavy presumption that the term "anti-CD20 antibody" carries its full ordinary and customary meaning.  The majority concludes that Biogen's statements during prosecution were sufficient.  In particular, the majority observes that:

[R]ather than challenging the examiner's understanding of the crucial terms, the applicants argued that the specification was enabling for anti-CD20 antibodies with similar affinity and specificity as Rituxan®.  Indeed, the applicants conceded that other "antibodies directed to the same antigen [i.e., CD20] might have different affinities and functional characteristics," and limited their claims to antibodies similar to Rituxan® nonetheless.  . . .  [I]t is clear that they were limiting their invention to what the examiner believed they enabled: antibodies that have a similar specificity and affinity for the specific epitope to which Rituxan® binds.

The majority also found both of Biogen's arguments regarding why the plain and ordinary meaning of the term should control to be unpersuasive.  First, in response to Biogen's argument of claim differentiation (that claim 1 broadly covers any and all anti-CD20 antibodies and several dependent claims are directed to specific types of antibodies, i.e., chimeric, rituximab, humanized, and human), the majority counters that "[o]ur cases make clear . . . that where found, prosecution history disclaimer can overcome the presumption of claim differentiation."  In response to Biogen's second argument that the '612 patent incorporates U.S. Patent No. 5,736,137, and that the '137 patent's broader definition of "anti-CD20 antibody" should control, the majority states that "[t]he problem with this argument is that the '137 patent expressly and uniquely defines 'anti-CD20 antibody' for use therein, that is, within the '137 patent."

Writing in dissent, Judge Plager states that "[b]ecause I do not find anywhere in the majority opinion or in the prosecution history that clear and unmistakable evidence of a disclaimer as required by our precedents, I cannot agree with the majority that such a disclaimer was made by Biogen during the prosecution of its application for the '612 patent."  Noting that "[t]he only dispute is whether the applicants disclaimed the plain meaning of 'anti-CD20 antibody' during prosecution," Judge Plager states that "[t]he majority purports to tease out of the prosecution history such a disclaimer."  The dissent continues:

Nowhere in the prosecution history did the applicants state that antibodies that bind to the same epitope on CD20 with similar affinity and specificity as RITUXAN® must be used, or that antibodies lacking those characteristics must not be used.  To the contrary, the applicants repeatedly made clear -- including in the same discussion as the allegedly disclaiming statement -- that because the invention was based on the discovery that anti-CD20 antibodies could treat CLL, the claimed methods were not limited to the use of any particular type anti-CD20 antibody.

"Because the district court's construction eviscerates the 'clear and unmistakable' requirement for prosecution disclaimer," Judge Plager states that he "cannot join the majority in affirming that erroneous construction."

Biogen Idec, Inc. v. GlaxoSmithKline LLC (Fed. Cir. 2013)
Panel: Circuit Judges Dyk, Plager, and Reyna
Opinion by Circuit Judge Reyna; dissenting opinion by Circuit Judge Plager

PBS NewsHour Examines Oral Argument in AMP v. Myriad -- Patent Docs Author Kevin Noonan Appears on Program

On Monday, the Supreme Court heard oral argument in Association for Molecular Pathology v. Myriad Genetics, Inc. (a transcript of the oral argument can be found here).  The PBS NewsHour examined yesterday's argument in a segment on Monday's program.  PBS senior correspondent Jeffrey Brown discussed the case with Marcia Coyle, chief Washington correspondent for The National Law Journal, as well as Ellen Matloff, Director, Cancer Genetic Counseling for the Yale Cancer Center, a plaintiff in the case; and Patent Docs author Dr. Kevin Noonan.  The NewsHour segment can be viewed below:

Watch Supreme Court Tackles Case of Patent Law, Human Genetics on PBS. See more from PBS NewsHour.

Myriad Genetic Database Under Siege

By Kevin E. Noonan --

With the U.S. Supreme Court set to consider the patent-eligibility of claims to isolated human DNA in AMP v. Myriad Genetics this morning, another aspect of Myriad’s control over BRCA testing technology is being contested.  As reported on Friday by Gina Kolata in the New York Times ("DNA Project Aims to Make Public a Company's Data in Cancer Genes"), a group headed by Dr. Robert Nussbaum, Chief of the Division of Genomic Medicine, University of California at San Francisco has started an effort to "recreate" Myriad’s database of mutations (in addition to those disclosed in its patents) that are predictive for increased risk of breast or ovarian cancer.

The genesis of this effort, termed Sharing Clinical Reports, stems from Myriad’s decision in 2004 to keep such information proprietary.  Myriad says its decision was based on misuse of the information in its database, which was intended for research use but was being used for patient diagnostics, a particularly sensitive area where such uncertainties can exist.  As a consequence of its patents restricting BRCA gene testing, Myriad has developed a proprietary database of such "new" mutations, including ones of "unknown significance" (i.e., that have not been associated with risk prognosis) as well as mutations having predictive capability.  (The Times article reports that the frequency of such "unknown significance" mutations was 40% in 1996, 20% in 2004 and 3% today, without attributing these figures.)  While there have been more than ten thousand basic research reports published in academic and medical journals since the time Myriad’s patents were granted, it is undoubtedly the case that there are undisclosed mutations known only to Myriad.

As reported in the Times, proponents of the effort are contacting physicians having patients who have received the Myriad test and thus have received a Myriad test report.  The requests are initially for the information to be donated, but the effort is sufficiently well funded that offers of thirty-three cents per report are being made.  (While that doesn’t sound like much, it might prove expensive if hundreds of thousands or millions of test reports were involved, as the article suggests.)  Reflecting the present informal nature of the effort, the article reports that the work of transmitting the patient test results is done by students "who need extra money" and that physicians who provide a minimum of 200 variants are rewarded with an Apple iPad mini.  Present funding is provided by Dr. Peter Kolchinsky, managing director of RA Capital Management in Boston (which should raise its own set of motivational questions in Ms. Kolata’s readers).

The article is, de riguer, replete with assertions that genetic researchers are "furious," and that Myriad is preventing second opinion testing (ironically, by the managing director of GeneDX, "a gene testing company working with Dr. Nussbaum").  [H]aving one company control the data for genes is contrary to the way medicine is developing," according to Heidi Rehm, a Harvard geneticist, who is reportedly also working with Dr. Nussbaum.  As detailed in the article, Dr. Rehm is apparently referring to "whole genome sequencing," which creates a situation where there are "22,000 genes" and "50 million variants" (which, even if true, is irrelevant to the subject under discussion, the two human BRCA genes and their mutations and variants).  And as might have been expected, the group is requesting the National Institutes of Health start a publicly funded database of all variants of all human genes studied.

Nonetheless, the group raises an important issue.  As has been reported here previously, one aspect of the gene patenting debate routinely ignored is that the genetic information is not patented.  Accordingly, the Sharing Clinical Reports effort is in no sense "illegal" (provided that the provisions of the Health Insurance Portability and Accountability Act, HIPAA, regarding patient confidentiality are not transgressed) nor should it raise patent infringement liability for the group.  If Myriad had amassed its database using proprietary means, or if trade secret misappropriation were involved, the company might have a way of preventing any effort to obtain the genetic data produced by such proprietary means.

Here, Myriad elected to enjoy the benefits of patent protection, wherein it could prevent anyone else from making, using, selling, offering to sell or importing its inventions.  In return, Myriad was required to disclose those inventions pursuant to the provisions of patent law that require a written description of the invention that enables a person of skill in the art to practice the invention after the patent(s) expire throughout the full scope of the claims, and to disclose the best mode of practicing the invention (the latter requirement having been significantly blunted by the Leahy-Smith America Invents Act).  And there is no allegation that Myriad did not properly satisfy these requirements, at least with regard to the mutations it had identified when it filed the applications that were eventually granted as its patents.

These disclosure requirements do not apply with regard to any "new" mutations contained in Myriad’s database, for the simple reason that they were unknown at the time these applications were filed.  Indeed, there is no requirement in patent law to supplement a patent specification unless new inventions are claimed.  But the advantages Myriad enjoys (and that "infuriate" the geneticists so) were procured based on the exclusivity provided by the patents, and these advantages will persist after the patents expire.  These facts raise the question of whether there is any aspect of this situation that would constitute "patent misuse," a concept used as a defense to a charge of patent infringement that involves (relevant to this discussion) extending patent exclusivity after the expiration of the patent term.  While the situation typically arises in patent licensing, it is reasonable to ask whether the policy drivers behind the defense have any relevance to the situation here, which can be expected to arise for any genetic diagnostic patents (exclusively or non-exclusively licensed), provided there is no obligation to make public or at least share new genetic information generated during the patent exclusivity period.

The answer is not to ban patents on isolated DNA (which are not infringed by genetic diagnostic methods in any event) or genetic diagnostic methods per se.  This is because the policy-based obligation, if any, arises from the patent grant itself and the quid pro quo of disclosure in exchange for such exclusivity.  Abolishing the exclusivity would abolish the obligation, and would provide incentives for companies to disclose as little information as possible.  Instead of identifying the mutations now sought by Dr. Nussbaum and his colleagues, for example, future (unpatented) genetic diagnostic methods could come merely with the information that a patient has a genetic mutation associated with an increased risk of a particular disease, with statistics on survival and treatment options and their success rates but no information on which mutation(s) were involved.  While this outcome would be even more inconsistent with the way genetic diagnostics is and has been developing than Myriad’s behavior bemoaned by Dr. Rehm in the article, what patients and their doctors want most are reliable diagnostic results, and a company offering such advanced diagnostics would be in a position to adopt a "take it or leave it" attitude regarding disclosure.  This possibility is even more likely for the majority of diseases that, unlike breast cancer and BRCA are multivariate and less readily reverse engineered.

These considerations are not amenable to judicial intervention (despite rumors that at least one of the legal proponents of the Myriad case is planning to file such a lawsuit).  Congress could intervene, but any bill would need to provide the right balance between return on investment (said to be more than $500 million by Myriad) and public access to information during and after the relevant patent term.  Any such attempt to legislate will also require less rhetoric and more problem solving than has been evident in the gene patenting debate, which in large part involves physicians demanding the right to freely infringe genetic patents in the name of patient rights.  Of course, none of these physicians is proposing to perform these tests for free, and that of course is one of the distinctions between these physicians and the researchers behind the 10,000 scientific research papers on the BRCA genes.  Regardless of the outcome of the Myriad case before the Supreme Court (which, no matter how it turns out, will have little to no effect on availability of genetic diagnostic testing for the BRCA genes), addressing the policy considerations involving human genetic diagnostics is something that will remain.  While the politics of confrontation generates headlines and contributions to those who paint themselves as patient champions, it has done and will do little to resolve these important issues.

Court Report

By Sherri Oslick --

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

Shire LLC v. Neos Therapeutics, Inc.
3:13-cv-01452; filed April 11, 2013 in the Northern District of Texas

Infringement of U.S. Patent Nos. RE42,096 ("Oral Pulsed Dose Drug Delivery System," issued February 1, 2011) and RE41,148 (same title, issued February 23, 2010) following a Paragraph IV certification as part of Neos filing of an NDA (under § 505(b)(2) of the Food, Drug and Cosmetic Act) to manufacture a generic version of Shire's Adderall XR® (a combination of dextroamphetamine saccharate, amphetamine aspartate monohydrate, dextroamphetamine sulfate, and amphetamine sulfate, used to treat attention deficit hyperactivity disorder).  View the complaint here.

Japanese Foundation for Cancer Research v. Rea et al.
1:13-cv-00412; filed April 1, 2013 in the Eastern District of Virginia

• Plaintiff:  Japanese Foundation for Cancer Research
• Defendants:  Teresa Stanek Rea; United States Patent and Trademark Office

Judicial review of the USPTO's refusal to grant a petition for withdrawal of an unauthorized disclaimer of the remaining term of U.S. Patent No. 6,194,187 ("Apoptosis-inducing Protein and Gene Encoding the Same," issued February 27, 2001).  View the complaint here.

Conference & CLE Calendar

April 15, 2013 - Association for Molecular Pathology v. Myriad Genetics post argument discussion (American University Washington College of Law Program on Information Justice & Intellectual Property and Federal Circuit Bar Association) - 4:30 to 5:50 pm (Eastern)

April 15-16, 2013 - China IP Counsel Forum (American Conference Institute) - Shanghai, China

April 16, 2013 - Myriad Debrief: Biotechnology and Patents before Supreme Court (John Marshall Law School) - Chicago, IL

April 16, 2013 - 29th Annual Joint Patent Practice Seminar (Connecticut, New Jersey, New York, and Philadelphia Intellectual Property Law Associations) - New York, NY

April 16, 2013 - Optimizing the Discovery Process: Home and Abroad (McDonnell Boehnen Hulbert & Berghoff LLP) - 10:00 to 11:15 am (CT)

April 17, 2013 - Myriad: The U.S. Supreme Court Argument (Intellectual Property Owners Association) - 2:00 - 3:00 pm (ET)

April 17, 2013 - European Biotech Patent Law Webinar (D Young & Co) - 4:00 am, 7:00 am, 12:00 pm (EDT)

April 17-19, 2013 - Corporate Patent Seminar (CPS) - Chicago, IL

April 18, 2013 - Advanced AIA Issues for Patent Claim Construction: Best Practices Absent Clear Court Guidance (Strafford) - 1:00 - 2:30 pm (EDT)

April 22-25, 2013 - 2013 BIO International Convention (Biotechnology Industry Organization) - Chicago, IL

April 30, 2013 - CincyBIO (CincyIP) - Cincinnati, OH

May 7-8, 2013 - Paragraph IV Disputes (American Conference Institute) - New York, NY

May 14, 2013 - Forum on Pharma & Biotech Collaborations (C5 (UK)) - Frankfurt, Germany

May 14-16, 2013 - Fundamentals of Patent Prosecution 2013: A Boot Camp for Claim Drafting & Amendment Writing (Practising Law Institute) - Chicago, IL

May 15-16, 2013 - Forum on Freedom to Operate (C5 (UK)) - Frankfurt, Germany

May 21-23, 2013 - Pharma Legal Affairs (IBC Life Sciences) - Shanghai, China

June 12-14, 2013 - Fundamentals of Patent Prosecution 2013: A Boot Camp for Claim Drafting & Amendment Writing (Practising Law Institute) - New York, NY

July 10-12, 2013 - Fundamentals of Patent Prosecution 2013: A Boot Camp for Claim Drafting & Amendment Writing (Practising Law Institute) - San Francisco, CA

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

John Marshall Law School Myriad Debrief

The John Marshall Law School will be hosting a Hot Topics in Intellectual Property Law seminar entitled "Myriad Debrief: Biotechnology and Patents before Supreme Court" from 9:00 to 10:00 am (Central) on April 16, 2013 at the John Marshall Law School in Chicago, IL.  Patent Docs author Kevin Noonan of McDonnell Boehnen Hulbert & Berghoff LLP will offer his insights on this critical case and debrief attendees on the oral argument to be held on April 15.  Those interested in registering for the seminar can do so here.

IPO Webinar on Oral Argument in Myriad

The Intellectual Property Owners Association (IPO) will offer a one-hour webinar entitled "Myriad: The U.S. Supreme Court Argument" on April 17, 2013 beginning at 2:00 pm (ET).  A panel consisting of Ned Israelsen of Knobbe Martens Olson & Bear, LLP; Prof. Joshua Sarnoff of the DePaul University College of Law; and Stuart Watt of Amgen Inc. will discuss the Justices' questioning during oral argument in AMP v. Myriad, will attempt to predict an outcome, and will outline possible industry responses.

The registration fee for the webinar is $120 (government and academic rates are available upon request).  Those interested in registering for the webinar can do so here.

CincyBio 2013

CincyIP will be holding its third CincyBIO conference on April 30, 2013 at the Phoenix in Cincinnati, OH.  The conference will consist of the following sessions:

• Exelixis and Novartis -- Biopharm Patent Term Adjustment Based on (B) Delay;
• New FDA Regulations and Their Effect on Existing and Emerging Technologies;
• Cintrifuse: Working with Technology Startups and Developing Cincinnati's Innovation Ecosystem;
• University Intellectual Property: The Tech Transfer Perspective;
• The Exhaustingly Self-Replicating Seeds: Monsanto v. Bowman; and
• Gene: The New Four-Letter Word.

Additional information about the conference can be found here, and an agenda and list of speakers for the conference can be found here.

There registration fee for the conference is $125 (CincyIP member), $150 (non-member with CLE), $100 (non-member without CLE), or $25 (students).  Those interested in registering can do so here.

Washington College of Law Post Argument Discussion of AMP v. Myriad

As part of its ongoing Supreme Court series, the American University Washington College of Law Program on Information Justice & Intellectual Property, along with the Federal Circuit Bar Association, will be hosting a post argument discussion on the Association for Molecular Pathology v. Myriad Genetics case from 4:30 to 5:50 pm (Eastern) on April 15, 2013 at the American University Washington College of Law in Washington, DC.  The Myriad panel discussion will be moderated by Jorge Contreras, American University Washington College of Law, with a panel consisting of Chris Hansen, American Civil Liberties Union Foundation, Counsel for Petitioners; Joshua Sarnoff, Center for Intellectual Property Law and Information Technology, DePaul University College of Law, Counsel for Amici, Fifteen Law Professors; Matthew Dowd, Wiley Rein LLP, Counsel for Amicus, James D. Watson, Ph.D.; Barbara Rudolph, Finnegan, Henderson, Farabow, Garrett & Dunner, LLP, Counsel for Amicus, American Intellectual Property Law Association; Arti Rai, Duke University School of Law.

Additional information about the post argument discussion, including registration/CLE information and information about the live and archived webcast, can be found here.

A Response to Dr. Mason's "Rebuttal" to Criticisms of His Genomics Medicine Article

By Kevin E. Noonan --

Much of the gene patenting debate has appeared, to experienced patent practitioners, to be akin to a conversation with Kevin Kline's character in A Fish Called Wanda, or perhaps a passage from P.G. Wodehouse's The Luck of the Bodkins.  In short, it has been the tale of doctors, scientists, and legal academics interpreting claims to isolated DNA in ways both bizarre and unlikely to anyone with any experience in actually claiming DNA.  However, as Dr. Mason's response illustrates those of us on the patent side of the debate have contributed to the confusion.

Reviewing Dr. Mason's assessment of the patents and applications he identified as encompassing almost the entirety of the human genome reveals two sources of misunderstanding.  The first is between the disclosure of patent specifications and the claims:  while sometimes in their zeal to provide the broadest disclosure possible, patent practitioners have been overly expansive in defining the scope of the isolated nucleic acids that are the subject of their clients' inventions, the claims have typically been more circumspect.  Most claims to isolated DNA have the canonical structure:

An isolated nucleic acid/human DNA molecule, encoding an amino acid sequence identified by SEQ ID NO. X.

Occasionally the word "comprising" is used in such claims:

An isolated nucleic acid/human DNA molecule, comprising a nucleotide sequence encoding an amino acid sequence identified by SEQ ID NO. X.

And there are claims to oligonucleotides, usually dependent on the claimed sequence:

An oligonucleotide comprising about 15 nucleotides of SEQ ID NO: X.

Considered in a vacuum, in the context of definitions as illustrated in Dr. Mason's response, it could be thought that such claims encompass a greater scope than they actually do.  What is missing is context, both historical and legal, that provides the insights needed to properly understand the scope of these claims.

The base canonical form above was developed about thirty years ago, during the age when "cloning" a DNA molecule that encoded a protein of interest (erythropoietin, tissue plasminogen activator, blood clotting Factor VIII, interferon, etc.) was a Herculean feat, and such claims were expressly directed towards full-length versions of these genes.  In the days before the Human Genome Project and the vast amount of genetic information it produced, such cloned genes had but one utility:  to permit the production of recombinant cells that expressed the gene product, typically to be used as one of the first "biologic" drugs.  In order for the claimed DNA molecule to have that utility, however, what was required almost always was that the full-length gene be isolated, because truncated proteins could not be expected to have the desired biological properties (and could have deleterious ones, such as increased immunogenicity or reduced half-life).  Accordingly, such claims do not have the scope Dr. Mason ascribes to them, because any such claim would be invalidated for failing to have the necessary utility.

Moreover, the scope of such claims are extremely narrow, being limited to isolated DNA molecules that encode the specifically recited amino acid sequence identified as SEQ ID NO: X.  An isolated human DNA comprising any change in this encoded amino acid sequence is not exclusive to the patentee and can be performed freely without literal infringement liability by anyone.  (The availability of the doctrine of equivalents for isolated human DNA claims is severely limited by U.S. Patent and Trademark Office practice in interpreting the application of 35 U.S.C. § 112(a) to such claims, and by ensuing prosecution history estoppel.)

The significance of this limitation in scope of isolated DNA claims can be understood by the following example.  If the single change in the amino acid sequence expressly recited in the claim is from a valine (Val) residue to an isoleucine (Ile) residue, the number of atoms in the protein would be increased by a mere 3 atoms (the difference in structure between these two amino acids is a methylene group,-CH₂-) out a total of 50-100,000 atoms in the protein.  Yet, even such a molecule changed to such a small degree would not literally infringe the generic claim.  Similarly, insertions or deletions of the sequence, mutations and sequence variants (naturally occurring or man-made) do not fall within the scope of claims to a specific, particular isolated human DNA, due to this restricted scope.  Such claims reciting such full-length "genes" are simply not preclusive of any other gene in the genome.

Turning to the oligonucleotide claims, there are two issues.  First, the work of Bob Cook-Deegan and his collaborators have shown (Kepler et al., "Metastasizing patent claims on BRCA1") that oligonucleotides on the order of 15-16 nucleotide residues in length are much more ubiquitous in the genome than was once thought.  This stems from the simplistic and incorrect assumption that any sequence of n nucleotides will occur once per 4ⁿ times in the genome.  Thus, the random 15-mer was expected to arise once every 1,073,741,824 basepairs, and the random 16-mer once every 4,294,967,296 basepairs.  The (false) conclusion was that in a haploid genome comprising 3 x 10⁹ basepairs, the 15-mer and 16-mer (and larger species) would be unique.  The source of the error is that human DNA is a historical molecule, and that many sequence motifs would be expected to arise many more times than random statistics would predict; the Human Genome Project (and basic biology) illustrates the fact that the human genome evolved by gene duplication and recombination, so that certain motifs (the ATP-binding cassette sequences, for example) sharing certain amino acid sequence and thus the nucleotide sequences encoding them, are much more common that was predicted.  The consequence of this biological fact is not that claims to such oligonucleotide encompass the entirety of the genome.  Rather, it is that claims of this scope are invalid, since the prior art is much more replete with these sequences than was expected.

The other distinction that should be appreciated is that what is disclosed (and even claimed) in patent applications does not raise infringement issues.  Indeed, filing overbroad claims in International Applications can be a strategic decision, to produce prior art against competitors (this stratagem became available in the U.S. with publication of U.S. applications under the American Inventor Protection Act of 1999).  Mere inspection of the published patent application database can find patents to a variety of "inventions" unlikely to ever grant with patentable claims, and their existence is thus not relevant to a serious debate over the scope of patents claiming isolated human DNA.

It is difficult to avoid the conclusion that a failure to appreciate these distinctions informs much of the angst enunciated by Dr. Mason and other physicians and researchers confronted by the prospect of infringement liability (or at least the fear that threats from patent holders will inhibit progress in genetics research).  But the patent community is not entirely blameless either, as illustrated by Dr. Mason in his Rebuttal.  There exists a certain amount of loose language in patent specifications that creates understandable confusion as to the claim scope the patentee believes she is entitled to, and thus uncertainty as to whether claims will be asserted as broadly as these specifications can be interpreted to support.  (Of course, some have interpreted these claims to encompass isolated DNA itself, an interpretation that would render the claims unpatentable since the time of Friedrich Miescher's work in the 19th Century.)  Some comfort should be taken by the fact that no gene patent holder has ever asserted claims to this extent, and that any attempt to do so would likely result in invalidation of the claims.  And the patent case law has provided more and more illustrations of claims (including Myriad's method claims) being interpreted in view of these overbroad specifications and invalidated based on broad claim construction.  In short, while there may be specifications suffering from symptoms of overbroad disclosure, the disease is self-correcting (even more so with the post-grant review and inter partes review provisions of the Leahy-Smith America Invents Act).

What is clearly needed is more dialog (and perhaps fewer assumptions) from both physicians and the patent community.  This debate comes thirty years too late to be particularly meaningful to claims to isolated nucleic acids.  But as the complexities of "modern" gene-based inventions increase (and their capacity to be ever more resistant to reverse engineering), the potential to eschew patent protection will increase, with the concomitant reduction in disclosure of biologically relevant inventions.  Such a trend, and Supreme Court decisions that promote that trend, particularly if based on unrealistic apprehensions over the (vanishingly small) possibility that claims to isolated human DNA will negatively impact developing genetic technologies, could paradoxically promote the outcome that opponents of gene patenting purportedly are committed to prevent.

A Primer on Claim Construction -- Comments on Dr. Mason's Response

By Donald Zuhn --

Yesterday, we posted a response from Dr. Chris Mason of Cornell University to a recent Patent Docs post and an article posted by Dr. Chris Holman on Holman's Biotech IP Blog.  Dr. Mason co-authored an article in the current issue of Genome Medicine, which contends that due to the non-specificity of sequence uniqueness across the genome and the broad scope of claims to nucleotide sequences, the Supreme Court and Congress should limit the patenting of existing nucleotide sequences.  In his response, Dr. Mason comments on several aspects of the Holman and Patent Docs posts, which he says suggest that the analysis from his paper "was mistaken or did not embody an accurate characterization of the claims' construction."

In response to Dr. Holman's assertion that Dr. Mason and his co-author Jeffrey Rosenfeld "seem to assume that every patent with a claim mentioning a gene sequence also claims every 15mer present in the sequence," Dr. Mason states that the authors did not make such an assumption, and that their paper instead describes the results of two distinct analyses.  In the first analysis, the authors "examined the uniqueness of 15mers in general, which was shown to be exceedingly non-unique genome-wide."  However, as we noted in our first post on Dr. Mason's paper, the conclusion regarding the broad scope of claims to 15mers -- and in particular claims 5 and 6 of Myriad's U.S. Patent No. 5,747,282 -- is not particularly ground-breaking given that Kepler et al. similarly concluded in a 2010 Genomics paper that claim 5 of the '282 patent was "exceptionally broad" (see "Caught in a Time Warp: The (In)validity of BRCA1 Oligonucleotide Claims").  Kepler et al. also suggested that "if human genes were random strings of nucleotides, one would expect a human gene to contain an average of 15 15-mers claimed under the ['282] patent," and in fact found that 80% of 713 human mRNAs deposited in 1994 (the earliest effective filing date of the '282 patent is August 12, 1994) contained at least one of the claimed 15mers.

With respect to their second analysis, Dr. Mason states that the authors "used patents that claimed 15mer sequences in their construction, and we indicated the matches we could find given their sequence composition."  Unfortunately, given Dr. Mason's views regarding the subject matter encompassed by the claims of U.S. Patent No. 7,795,422 -- one of "58 patents [according to Dr. Mason] whose claims covered at least 10% of the bases of all human genes," and a patent Dr. Mason labeled as their "top patent . . . whose claims' sequences matched 91.5% of human genes" -- it is not entirely clear what Dr. Mason means when he says that the authors "used patents that claimed 15mer sequences in their construction" (emphasis added).  An analysis of the claims in the '422 patent, as well as those in U.S. Patent No. 7,468,248 (a second patent discussed in the Genome Medicine article), clearly indicates that Dr. Mason's top two candidates do not contain "explicit claims for 15mers that matched 84% of human genes," as asserted in his paper (assuming that by "explicit claims," Dr. Mason means that the claims cover or encompass 15mers).  It is also abundantly clear from both the Genome Medicine paper and his subsequent response that Dr. Mason does not understand the process of claim construction (which is not surprising given that Dr. Mason is not a patent practitioner).

So, what follows is a short primer on claim construction.  Claim construction is the process of giving proper meaning to the language of the claims.  Abtox Inc. v. Exitron Corp., 122 F.3d 1019, 1023 (Fed. Cir. 1997).  The language of the claim frames and ultimately resolves all issues of claim interpretation, since it is the language of the claim that defines the scope of the protected invention.  Id.  However, in determining the scope and meaning of a claim term, three additional sources may be considered:  the descriptions in the rest of the patent specification, the prosecution history, and relevant extrinsic evidence.  Phillips v. AWH Corp., 415 F.3d 1303, 1315, 1317 (Fed. Cir. 2005).

With regard to the use of the specification and prosecution history to construe claim terms, the Federal Circuit has stated that:

Claims must be read in view of the specification, of which they are a part.  The specification contains a written description of the invention that must enable one of ordinary skill in the art to make and use the invention.  For claim construction purposes, the description may act as a sort of dictionary, which explains the invention and may define terms used in the claims.  . . .  The written description part of the specification itself does not delimit the right to exclude.  That is the function and purpose of the claims.

To construe claim language, the court should also consider the patent’s prosecution history[.]  . . .  Although the prosecution history can and should be used to understand the language used in the claims, it too cannot "enlarge, diminish, or vary" the limitations in the claims.

Markman v. Westview Instruments, Inc., 52 F.3d 967, 979-80 (Fed. Cir. 1995) (in banc), aff’d, 517 U.S. 370 (1996) (citations omitted).

In Phillips, the Federal Circuit noted that where the intrinsic evidence (i.e., claim language, specification, and file history) does not resolve ambiguity in the meaning of a claim term, a court may also consider extrinsic evidence, such as expert testimony, dictionaries, and treatises.  Phillips, 415 F.3d at 1317-19.  Such "extrinsic evidence can help educate the court regarding the field of the invention and can help the court determine what a person of ordinary skill in the art would understand claim terms to mean."  Id. at 1319.

With the above legal principles in mind, we turn back to the claims of the '422 and '248 patents.  The '422 patent contains five claims, only one of which is an independent claim (i.e., does not depend from, and include the limitations of, another claim):

1.  A chemically modified short interfering nucleic acid (siNA) molecule, wherein:
    (a) the siNA molecule comprises a sense strand and an antisense strand, each strand having one or more pyrimidine nucleotides and one or more purine nucleotides;
    (b) each strand is independently 18 to 27 nucleotides in length, and together comprise a duplex having between 17 and 23 base pairs;
    (c) the antisense strand is complementary to a human Hypoxia Inducible Factor 1 (HIF1) RNA sequence comprising SEQ ID NO:567;
    (d) a plurality of pyrimidine nucleotides present in the sense strand are 2'-deoxy-2-fluoro pyrimidine nucleotides and a plurality of purine nucleotides present in the sense strand are 2'-deoxy purine nucleotides; and
    (e) a plurality of pyrimidine nucleotides present in the antisense strand are 2'-deoxy-2'-fluoro pyrimidine nucleotides and a plurality of purine nucleotides present in the antisense strand are 2'-O-methyl-purine nucleotides.

A cursory analysis of claim 1 (a more thorough analysis being unnecessary) indicates that the claim is directed to a "chemically modified short interfering nucleic acid (siNA) molecule."  Therefore, claim 1 does not cover or encompass molecules other than chemically modified short interfering nucleic acids (siNAs).  More importantly, the siNA molecules that are covered or encompassed by claim 1 must possess a sense strand having "a plurality of pyrimidine nucleotides [that] are 2'-deoxy-2-fluoro pyrimidine nucleotides," and an antisense strand having "a plurality of pyrimidine nucleotides [that] are 2'-deoxy-2'-fluoro pyrimidine nucleotides."  2'-deoxy-2'-fluoro pyrimidine nucleotides are not naturally-occurring nucleotides.

In response to Dr. Holman's statement that "DNA does not contain 2'-deoxy-2-fluoro pyrimidine nucleotides and 2'-deoxy purine nucleotides," Dr. Mason notes that "'2'-deoxy purine nucleotides' are simply the 'A' and 'G' nucleotides in normal DNA."  He does not, however, contend that 2'-deoxy-2'-fluoro pyrimidine nucleotides are found in "normal DNA."  Dr. Mason also takes Patent Docs to task for stating that "the lone independent claim of the '422 patent is directed to a 'chemically modified' double-stranded nucleic acid molecule," and "[i]t is therefore difficult to see how the claimed sequences of the '422 patent could 'match[] 91.5% of human genes.'"  Dr. Mason counters that "[i]t is notable that one of the claimed chemical modifications allowed from [the '422 patent] claims is '2'-deoxyribonucleotides,' which is the same thing as dexoyribonucleotides, or DNA."  However, as noted above, the siNA molecules of claim 1 of the '422 patent must possess a sense strand having "a plurality of pyrimidine nucleotides [that] are 2'-deoxy-2-fluoro pyrimidine nucleotides," and an antisense strand having "a plurality of pyrimidine nucleotides [that] are 2'-deoxy-2'-fluoro pyrimidine nucleotides."  And 2'-deoxy-2'-fluoro pyrimidine nucleotides are not naturally-occurring nucleotides found in "normal DNA."  Dr. Mason also lists "six other potential embodiments (of many) from [the '422] patent that could easily cover unmodified bases or fragments thereof," adding that "[t]he claims must be interpreted in plain language first, of course, but also in light of their specifications of the patent."  Notwithstanding the importance of the specification in claim construction, absent a clear and specific statement giving a claim term a special definition, that term should be construed as having the plain and ordinary meaning given by persons experienced in the field of the invention.  Renishaw plc v. Marposs Societa' per Azioni, 158 F.3d 1243, 1249 (Fed. Cir. 1998).  Therefore, the disclosure in the '422 patent specification of unclaimed embodiments such as unmodified siNA molecules does not trump the express recitation in claim 1 of "[a] chemically modified short interfering nucleic acid (siNA) molecule" possessing a sense strand having "a plurality of pyrimidine nucleotides [that] are 2'-deoxy-2-fluoro pyrimidine nucleotides," and an antisense strand having "a plurality of pyrimidine nucleotides [that] are 2'-deoxy-2'-fluoro pyrimidine nucleotides."  Thus, contrary to Dr. Mason's assertion, the claims of the '422 patent do not "claim[] 15mer sequences."

The same is true for the claims of the '248 patent.  As we noted in our last post, the claims of the '248 patent are directed to methods of inferring a trait of a bovine subject, determining a nucleotide occurrence of a polymorphism in a bovine sample, and identifying a bovine single nucleotide polymorphism (SNP) associated with a trait, and not 15mer nucleic acid molecules.  In response to Dr. Holman's observation that the independent claims of the '248 patent are method claims, Dr. Mason agrees, but suggests that "their specifications allow for a broad interpretation."  However, the disclosure of "an isolated polynucleotide that includes at least 20 contiguous nucleotides of any one of SEQ ID NOS:24493 to 64886" in the specification simply does not convert a claim directed to a method into a claim directed to a oligonucleotide.  As with the '422 patent, therefore, the claims of the '248 patent simply do not "claim[] 15mer sequences."

To put the above in layman's terms, Dr. Mason could make or use a 15mer derived from the human Hypoxia Inducible Factor 1 (HIF1) RNA sequence comprising SEQ ID NO:567 or the nucleotide sequence of SEQ ID NO:21645 and not be found liable for infringing either the '422 or '248 patents -- provided, of course, that he was not using either sequence to generate the claimed siNA of the '422 patent or practice the claimed methods of the '248 patent.

In his response, Dr. Mason argues that even if one disagrees with his analysis of the '422 patent, related U.S. Patent No. 8,273,866 supports his assertions.  Claim 1 of the '866 patent recites:

1.  A short interfering RNA (siRNA) molecule having a sense strand and an antisense strand that mediates RNA interference, wherein:
    (a) each strand is between 18 and 24 nucleotides in length;
    (b) the sense strand comprises 10 or more 2'-deoxy, 2'-O-methyl, 2'-deoxy-2'-fluoro, or universal base modified nucleotides, and a terminal cap molecule at the 3'-end, the 5'-end, or both 3' and 5'-ends of the sense strand;
    (c) the antisense strand comprises 10 or more 2'-deoxy, 2'-O-methyl, 2'-deoxy-2'-fluoro, or universal base modified nucleotides; and
    (d) 10 or more pyrimidine nucleotides of the sense and antisense strand are 2'-deoxy, 2'-O-methyl or 2'-deoxy-2'-fluoro nucleotides.

Dr. Mason argues that "any sequence that is 18-24 bases can be constructed from these claims, [and] this may mean that every single 18-24mer is potentially claimed by this patent."  Not quite.  Claim 1 is directed to "[a] short interfering RNA (siRNA) molecule having a sense strand and an antisense strand that mediates RNA interference."  A "single 18-24mer" is not "[a] short interfering RNA (siRNA) molecule having a sense strand and an antisense strand that mediates RNA interference."

Turning back to Dr. Mason's response, he counters Dr. Holman's assertion that the 15mer claims of Myriad's '282 patent are "extremely rare" by pointing out that "[a]fter searching for a short time on Google Patents, I was able to find two potential examples of recently published patent applications that directly claim a large subset of genes."  As noted in an editorial comment to Dr. Mason's response, the response was revised per Dr. Mason's request to indicate that the documents Dr. Mason identified were published patent applications rather than patents as he stated in the original version of his response.  However, it is unclear whether Dr. Mason understands that identifying two "published patent applications" as "issued patents" was not merely an unfortunate typographical error.  Instead, Dr. Mason's citation of two published patent applications provides no support for his argument that 15mer claims can be readily found in recently issued patents because infringement liability arises only when an individual "without authority makes, uses, offers to sell, or sells any patented invention" (35 U.S.C. § 271(a)), and the published patent applications he cites are not patents.

Finally, when defending the assertion in paragraph 10 of his Declaration that "Claim #1 and #2 of '282 are so broad that they can include up to 100% of the genes in the human genome," Dr. Mason counters with more of the same flawed argument.  He first notes that "55% homology is a very low threshold," and then points to claim 6, which is directed to "[a]n isolated DNA having at least 15 nucleotides of the DNA of claim 2."  But claims 1 and 2 do not recite 15mer fragments of DNA encoding the amino acid sequence of SEQ ID NO:2 or the nucleotide sequence of SEQ ID NO:1 that share 55% identity with those sequences.  Instead, claims 1 and 2 are directed to a nucleic acid encoding a protein of 1863 amino acids and a nucleic acid of 5914 nucleotides.