Friday, December 19, 2014

Myriad II: Another Blow to the Patenting of Biotech Innovation


On December 17 the Federal Circuit issued a unanimous decision invalidating product and method claims relating to BRCA genetic diagnostic testingfor lack of patent eligibility. The decision, formally titled In re BRCA1- & BRCA2- Based Hereditary Cancer Test Patent Litigation, University of Utah Research Foundation v. Ambry Genetics Corp, has been referred to as “Myriad II,” since it involves the same patents that were at issue in “Myriad I,” the Supreme Court’s landmark 2013 decision (although the two cases involve different claims).  Myriad II is yet another blow to the patenting of diagnostics and personalized medicine, and biotechnology innovation in general.
 
Background
Myriad I dealt primarily with two types of patent claims: product claims directed towards isolated DNA molecules, and method claims broadly ditected towards the comparison of a human subject’s BRCA gene sequence with the wild-type sequence. Early in the Myriad I litigation, the Federal Circuit declared the “comparison” method claims patent ineligible. The Supreme Court subsequently declared the product claims directed towards isolated genomic DNA molecules patent ineligible, while upholding the patent eligibility of claims directed towards isolated cDNA, which the Court characterized as man-made and sufficiently removed from their native counterpart to qualify for patent protection.

Myriad II picks up where Myriad I left off, by addressimg the patent eligibility of product and method claims that were not challenged by the plaintiffs in Myriad I, and which lie farther along the spectrum towards patent eligibility than the claims invalidated in Myriad I.  In particular, while the method claims in Myriad I merely recited a single step of “comparing” two DNA sequences, the method claims at issue in Myriad II further recite specific DNA analysis steps such as amplification by PCR or hybridization to a DNA probe.  The product claims in Myriad II are directed towards “pairs” of PCR primers, which are by definition synthetic molecules. In contrast, the product claims found to be patent ineligible in Myriad I were directed towards single DNA molecules, which were not necessarily synthetic (Myriad’s patent specifications defined “isolated” so as to encompass native origin genomic DNA).

Method Claims
The Federal Circuit’s invalidation of the method claims in Myriad II was unfortunate but not surprising.  Prior to the Supreme Court’s recent decisions in Mayo and Alice, many practitioners (including myself) would have thought that the inclusion of clearly patent eligible claim limitations (such as the use of hybridization probes and PCR amplification) would have rendered the claims clearly patent eligible.  In fact, this was the position taken by the Federal Circuit when it first decided Prometheus v. Mayo, when the court upheld the patent eligibility of what were essentially diagnostic method claims. However, in Mayo the Supreme Court reversed the Federal Circuit, holding that the inclusion of patent eligible claim limitations (i.e., administering a drug and determining level of metabolite) does not necessarily render a claim otherwise directed towards a fundamental principle (i.e., a natural phenomenon, law picture or abstract ideas) patent eligible, if the patent eligible limitaations are “well understood, routine and conventional.”

In Myriad II, the Federal Circuit characterized the comparison of subject and wild-type DNA sequences to be an abstract idea, which contrasts with Mayo, wherein the physiological correlation at the heart of the claims was characterized as a natural phenomenon. But whether characterized as an abstract idea or natural phenomenon, the ultimate question under the new patent eligibility jurisprudence (Mayo and Alice) is whether additional claim limitations introduce sufficient “further ‘inventive concept’ to take the claim into the realm of patent eligibility.” In Myriad II, the Federal Circuit determined that the use of hybridization probes and PCR in genetic diagnostics is “well understood, routine and conventional,” and thus insufficient to render the claim patent eligible.
This is precisely what happened in Ariosa Diagnostics v. Sequenom, a district court decision I discussed in a previous post. Ariosa Diagnostics is currently on appeal to the Federal Circuit. It will be interesting to see how that case is decided, but based on the decisions in Mayo and now Myriad II, it seems likely that the district court’s decision will stand.

An interesting side note: In Myriad I, Judge Bryson of the Federal Circuit identified specific method claims in Myriad’s patents that were not at issue in Myriad I, but which Judge Bryson assumed would be patent eligible. His point was that Myriad did not need the patent claims at issue in Myriad I in order to protect its business, since alternative (presumably valid) claims would nonetheless be available for the company. In writing the opinion of the Supreme Court majority in Myriad I, Justice Thomas specifically cited to Judge Bryson’s remark, opining that Myriad was in an excellent position to obtain alternative patent claims which presumably would be valid and would provide adequate protection.

In Myriad II, Myriad pointed to these statements by Justice Thomas and Judge Bryson, and argued that its method claims are very similar to a claim specifically identified as patent eligible by Judge Bryson. Judge Dyk (author of Myriad II) rejected this argument, but it seems clear that under the Federal Circuit’s analysis as set forth in Myriad II, the claim which Judge Bryson and Justice Thomas assumed to be patent eligible is in fact not patent ineligible.
In other words, it appears that Judge Bryson and Justice Thomas (and likely other Justices on the Supreme Court) decided Myriad I on the basis of a flawed premise, i.e., that their decision would not fundamentally undercut the ability of companies like Myriad to effectively patent their inventions. Unfortunately, that is not the way the Court’s patent eligibility jurisprudence is playing out.

Product Claims
In Myriad II, Myriad essentially argued that the Supreme Court’s holding in Myriad I should be read as limited to isolated DNA molecules of native origin, and not extending to synthetic DNA molecules such as the claimed PCR primers. I think that this was a reasonable argument - the isolated DNA claims invalidated by the Supreme Court encompassed native DNA, i.e., DNA isolated from human tissue. In Myriad I the Court never explicitly addressed the patent eligibility of a claim limited to synthetic genomic DNA.  Still, most people (including the PTO) have inferred that Myriad I applies to synthetic versions of naturally occurring DNA (and other biomolecules), so it was not surprising that the Federal Circuit rejected Myriad’s argument and held that the synthetic nature of the claimed PCR primers was insufficient to render them patent eligible.

What I found more significant with respect to the PCR primer claims is that the claims were directed towards a combination of primers, rather than to a single isolated DNA molecule.  It’s one thing to declare isolated natural products patent ineligible; it’s quite another to declare combinations of natural products patent ineligible. After all, at some level most product claims are directed towards inventive combinations of natural products.

For example, the foundation of biotechnology is recombinant DNA, which typically involves involved the recombination of naturally occurring genetic elements. It cannot be the case that any combination of synthetic versions of naturally occurring biomolecules is patent ineligible, but in Myriad II the Federal Circuit provides no guidance with respect to the threshold for patent eligibility.

Interestingly, patent eligibility guidance published by the PTO on March 4, 2014 (which the PTO refers to as the “March 2014 Procedure”) included a specific example of a claim directed towards a pair of PCR primers, and concluded that the claim was not patent eligible because the sequence of the primers is the same as naturally occurring DNA. I always found this example particularly problematic, because it failed to acknowledge the distinction between a claim directed toward a natural product and a claim directed toward a nonnaturally occurring combination of natural products.

The PTO’s most recent “Interim Eligibility Guidance” (published December 16, 2014) specifically supersedes the March 2014 Procedure, and does not include the PCR primer claim example. To the contrary, the Interim Eligibility Guidance specifically notes that “when [a] nature-based product is produced by combining multiple components, the markedly different characteristics analysis should be applied to the resultant nature-based combination, rather than its component parts.” (Emphasis added).

Unfortunately, in Myriad II, the Federal Circuit has essentially adopted the PTO’s original position in the March 2014 Procedure, focusing on the components recited in the PCR primer claims rather than the claimed combination. A step backwards, introducing more uncertainty into the misguided doctrinepatent eligibility , and in all likelihood more difficulties for biotechnology innovators seeking effective patent protection for their inventions.
 

Friday, November 1, 2013

Aria Diagnostics v. Sequenom: Genetic Diagnostic Claims Patent Ineligible


 
A recent decision out of the ND of California portends poorly for the patent eligibility of genetic diagnostic testing methods.

Sequenom is the exclusive licensee of US patent 6,258,540, which Sequenom licensed from Isis
Innovation Limited.  The patent relates to prenatal detection methods performed on a maternal serum or plasma sample from a pregnant female, which methods comprise detecting the presence of a paternally inherited nucleic acid of fetal origin in the sample, and is based on the discovery that cell-free fetal DNA (sometimes referred to as “cffDNA”) is detectable in maternal serum or plasma samples. The “invention enables non-invasive prenatal diagnosis, including for example sex determination, blood typing and other genotyping, and detection of pre-eclampsia in the mother.”


Ariosa, formerly known as Aria Diagnostics, sued Sequonom in the Northern District of California seeking a declaratory judgment that it does not infringe the ‘540 patent. On October 30, the court granted summary judgment in favor of Arioso, declaring a number of claims of the ‘540 patent invalid for being directed towards patent ineligible subject matter under 35 USC 101. The decision is available here.


Claim 1 is representative of the invalidated claims. It recites:

 
1. A method for detecting a paternally inherited nucleic acid of fetal origin performed on a maternal serum or plasma sample from a pregnant female, which method comprises:

amplifying a paternally inherited nucleic acid from the serum or plasma sample and

detecting the presence of a paternally inherited nucleic acid of fetal origin in the sample.

 
Recent Supreme Court decisions addressing patent eligibility, particularly Mayo v. Prometheus, have emphasized two criteria for assessing patent eligibility of method claims directed towards a practical application of the discovery of a “natural phenomenon.” First, does the claimed method add something to the natural phenomenon beyond what is already “well-understood, routine, or conventional.” Second, does the claimed method “preempt” the natural phenomenon.

 
With regard to the first criterion, the District Court interpreted the requirement of something more than well understood, routine and conventional activity as imposing a requirement that the claimed method must constitute an “inventive” application of the natural phenomenon. The court held that “use of a newly discovered natural phenomenon [] will not render a claim patentable if the use of that natural phenomenon, [] is the only innovation contained in the patent.”  The court found that the only inventive aspect of the method was the discovery of the presence of cffDNA in maternal plasma, and that the detection of cffDNA using conventional techniques for DNA detection was not sufficiently inventive to render the claim patent eligible.

 
One way of looking at it is that the court essentially conducted a nonobviousness analysis, usually the province of Section 103, under the guise of Section 101 patent eligibility, treating the newly discovered natural phenomenon which formed the basis for the claim method as something akin to prior art, and concluding that it was not inventive (i.e., it was obvious) to combine the natural phenomenon with prior art methods for DNA detection. It will be interesting to see how the Federal Circuit responds to this interpretation of the “well understood, routine and conventional” language the Supreme Court used in Mayo.  Unfortunately, it seems to comport with a literal reading of Mayo. However, in the Federal Circuit’s recent fractured en banc decision in CLS Bank Int’l v. Alice Chief Judge Rader authored an opinion explicitly stating that, in his view, the Supreme Court’s use of the language “well-understood, routine and conventional” does not inject a requirement of inventiveness into the section 101 patent eligibility analysis.  Other Federal Circuit judges offered different interpretations, and there appear to be some that are much more receptive to that the Supreme Court has injected an “inventiveness” criterion in the test for patent eligibility.

 
Regarding the second criterion, the District Court found that the claim would cover all “commercially viable” means of testing for paternal cffDNA and thus preempted use of the natural phenomenon.  Sequenom presented evidence that there are alternate methods available for detecting cffDNA  that are not covered by the claim, but the court characterized these methods as not “commercially viable,” and hence not relevant to its preemption analysis, which focused on the practical impact of the patent claims.  The decision suggests that a method claim such as this is patent ineligible unless, “at the time of the invention or at the time of issuance of the patent,” there are available commercially viable alternatives for applying the claimed natural phenomenon.

 
If the approach used by this court is upheld by the Federal Circuit and applied generally to diagnostic claims, it would seem to severely limit the availability of patent protection for diagnostics.   One well-known patent that immediately comes to mind is Genetic Technology Ltd’s so-called “junk DNA” diagnostic patent, US Patent No. 5,612,179, which involves diagnostic analysis of non-coding DNA and has been asserted against numerous alleged infringers. But even if this approach is adopted, there remains some reason to be optimistic with respect to personalized medicine claims, particularly if the claim includes a step actually applying diagnostic information, for example by administering a drug to a patient. I think the Federal Circuit’s recent decision in Classen Immunotherapies, Inc. v. Biogen IDEC would support that position.

Sunday, June 30, 2013

Judge Calls Anticancer Inc.’s Attempts to Enforce GFP Patents “Misguided,” Warns that Future Enforcement Activity Could Warrant an Award of Attorney’s Fees



On June 26, in the case of Anticancer, Inc. v. Leica Microsystems, Inc., a federal judge in the Southern District of California granted a motion for summary judgment against Anticancer Inc., finding that Anticancer had failed to raise a genuine issue of material fact with respect to the allegation that Leica Microsystems had induced the infringement of US patent numbers 6,649,159; 6,759,038; and 6,251,384.  (see the Court’s Order) The patents generally relate to the use of green fluorescent protein (GFP) as an indicator of promoter activity in research animals. The judge denied the defendants’ motion for attorneys fees, but just barely, characterizing Anticancer’s efforts to enforce its patent rights as “misguided.” Although the court did not find the level of “bad faith” necessary to award attorney’s fees, it suggested that if Anticancer continues to bring meritless lawsuits an award of attorney’s fees could be justified.

The defendant, Leica Microsystems, sells imaging equipment that presumably can be used in a manner thatAnticancer believes would infringe  its patents, but the mere act of selling an item that can be used to infringe a patent does not in and of itself constitute patent infringement. Under 35 USC 271(b) a party can be held liable for inducing its customers to infringe a patent, but in order to prevail under an inducement theory the patent owner must prove that the customers have directly infringed the patent, and that the customer's were induced to infringe by the defendant . In this case, the court found that Anticancer had failed to produce sufficient evidence to withstand summary judgment with respect to both elements, i.e., direct infringement by Leica's customers and inducement by Leica.

Anticancer’s purported evidence of direct infringement comprised numerous articles published by scientists at various universities and research institutes that reported the use of an instrument purchased from Leica. Anticancer attempted to establish infringement by means of an expert declaration, but the court found that the declaration did not raise a genuine issue of material fact with respect to direct infringement by the third-party researchers. The court pointed out that the expert declaration did not identify which of Anticancer's patent claims in particular were infringed by the methodologies described in the publications. Furthermore, the court noted that all of the allegedly infringe claims are method claims, and that the expert had not explained “how the papers cited reflect the performance of each step of the methods claimed, much less that they were performed in the required order.”

Anticancer’s purported evidence of inducement consisted largely of Leica promotional materials, such as press releases, articles and brochures used by the company to promote its products. The court found two critical problems with this evidence. First, and most importantly, Anticancer had failed to present any evidence that the third-parties who had allegedly infringe the patents had ever seen any of the promotional materials. Second, some of the evidence actually showed that the products could be put to noninfringing use.

The court denied Leica’s request for an award of attorney’s fees, essentially concluding that a determination of “bad faith” is required for an award of attorney’s fees, and finding insufficient evidence that Anticancer’s actions were sufficiently egregious to constitute bad faith. However, the court went on to note that this is the third case in which Anticancer’s claims of patent infringement have been resolved in the defendant’s favor on summary judgment, and that although “Plaintiff’s efforts to enforce its patent rights may, at this point, be misguided, a finding of bad faith may be warranted if Plaintiff continues to press claims that ultimately have no merit, especially if courts continue to rule against it on summary judgment based on failures similar to those in this case."


The judge’s comments regarding the potential for a finding of bad faith if Anticancer continues to attempt to enforce its patents in this manner brings to mind a recent New York Times op-ed authored by Chief Judge of the Federal Circuit Rader and law profs Colleen Chien and David Hricik.  These authors suggested that a way to deal with the problem of frivolous patent lawsuits (i.e., patent trolls) would be for the courts to make more use 35 USC 285 and Rule 11 of the Federal Rules of Civil Procedure to shift the cost of litigation from defendants to patent owners filing frivolous lawsuits. They reported that, according to their count, attorneys fees were shifted under Section 285 in only 20 out of nearly 3000 patent cases filed in 2011, a statistic they found to be “remarkable.” The district court judge in the Anticancer case seemed close to awarding attorneys fees to Leica, and perhaps with the encouragement of Chief Judge Rader the next district court judge considering an award of sanctions against Anticancer might actually pull the trigger.

 

 

 

Wednesday, June 26, 2013

In Myriad the Supreme Court Has, Once Again, Increased the Uncertainty of U.S. Patent Law



On June 13 the U.S. Supreme Court issued a unanimous decision in Association for Molecular Pathology v. Myriad Genetics (Myriad) which essentially upheld the patent eligibility of claims reciting cDNA molecules encoding BRCA proteins, but struck down as patent ineligible claims encompassing isolated fragments of BRCA-encoding genomic DNA. Unfortunately, as a consequence of the manner in which the case was decided Myriad will in all likelihood only serve to increase the ambiguity and uncertainty plaguing the U. S. patent system. Clearly, the mere isolation of a naturally occurring biomolecule is no longer sufficient to confer patent eligibility on the isolated product, regardless of how useful, nonobvious or inventive the isolated product is relative to the prior art. What is less clear is the patent eligibility status of a synthetic molecule that shares a common, or highly similar, structure with a naturally occurring biomolecule.
 I have written an article that addresses some of the ambiguities created by the Myriad decision, and the practical implications for patenting in the life sciences arena.  The article, which appears in Biotechnology Law Report, is available here for the interested reader.

Monday, May 13, 2013

Monsanto v. Bowman: A Unanimous Supreme Court Sides with Monsanto

 
 
Today a unanimous Supreme Court affirmed the Federal Circuit's decision in Monsanto v. Bowman, and held that "patent exhaustion does not permit a farmer to reproduce patented seeds for planting and harvesting without the patent holder's permission." A background on the case can be found in earlier posts to this blog.
The Justices seemed to see through Bowman's arguments and understand what was at stake in this case. Writing for the Court, Justice Kagan noted that it is "well-settled" that the authorized purchaser of a patented product does not acquire any right to make copies of the product, and observed that were the Court to find in favor of Bowman patents would provide "scant benefit" to companies like Monsanto, and little incentive for investment in innovation.
The Court’s decision is explicitly premised on the fact that Monsanto requires farmers to enter into a license agreement which allows them to plant the patented seeds and harvest the resulting crop for use as food or animal feed, but not to replant the seeds or sell them for replanting. In footnote 3, the Court points out that "we do not here confront a case in which Monsanto (or an affiliated seed company) sold Roundup Ready to a farmer without an express license agreement. For reasons we explain below, we think that case unlikely to arise. And in the event it did, the farmer might reasonably claim that the sale came within an implied license to plant and harvest one soybean crop."
Kagan pointed out that a decision in favor of Bowman would be entirely inconsistent with the Court’s 2001 decision in J.E.M Ag Supply v. Pioneer Hi-Bred International, in which the Court held that utility patent protection is available for seeds and plants. In J.E.M., the Court noted that that the requirements for getting a patent are more stringent than those for obtaining a Plant Variety Protection (PVP) certificate, and that the protections afforded by a patent are correspondingly greater.  If the Court had sided with Bowman, it would mean that the owner of a patent would not only not be able to prevent a buyer from saving and replanting harvested seeds, but would be unable to prevent the buyer from selling the seeds, something "even a PVP certificate owner (who, recall, is supposed to have fewer rights) can usually accomplish."
Some supporters of Bowman have argued that farmers have a long-standing tradition of buying commodity grain for planting, but the Court gave short shrift to this contention. In a footnote, the Court observed that grain elevators "purchase grain from farmers and sell it for consumption; under federal and state law, they generally cannot package or market their grain for use as agricultural seed." The Court also noted that the commodity soybeans Bowman purchased were not intended for planting, but for consumption, and that Bowman himself had "conceded in deposition testimony that he knew of no other farmer who employed beans bought from a grain elevator to grow a new crop."
The Court also rejected Bowman's argument that seeds should be treated differently for purposes of exhaustion because they "self-replicate." The Court observed that Bowman was far from a passive observer, and that he had actively "made" (in the infringing sense) the copied seeds by purchasing the seeds knowing that many would be Roundup Ready, applying glyphosate in a way that culled any plants without the patented trait, saving the seeds to plant a later time, planting the beans in his field at the time he thought best, attending and treating them, including by exploiting their patented glyphosate-resistance, and harvesting the seeds, which he either marketed or saved to begin the next cycle. "In all this, the bean surely figure. But it was Bowman, and not the bean, who controlled the reproduction (unto the eighth generation) of Monsanto's patented invention.”
In the final paragraph, Kagan emphasizes that the decision is limited to the facts on hand, and the holding does not extend to hypothetical situations in which an article self-replicates "outside the purchaser’s control," or in which replication might be a necessary or incidental step in using the item for another purpose. She cites to 17 USC  117, a section of the copyright statute that addresses concerns relating to software and copyright that are very analogous to the concerns about inadvertent infringement expressed by supporters of Bowman. This analogy between software copyright and DNA patent was the theme of the Amicus brief I filed in support of Monsanto, in which I particularly pointed out that concerns about unavoidable infringement could be addressed by Congress if necessary, and citing 17 USC 117 as a specific example of that approach.
 
 

Friday, May 10, 2013

Jury finds Cellectis meganuclease claims invalid, but infringed by Precision Biosciences under Doctrine of Equivalents



As reported in an earlier post, on March 1, 2011, Cellectis sued Precision Biosciences in the District Court of Delaware [CIV-No.-11-173] for allegedly infringing US patent number 7,897,372, directed to "I-CreI Meganuclease Variants with Modified Specificity.”   The companies are both attempting to commercialize engineered meganucleases for use in genetic engineering. The litigation between Cellectis and Precision Biosciences has come to include 20 distinct lawsuits filed in Delaware and Eastern North Carolina (Precision licenses its patents from Duke University), and to involve multiple patents owned by both companies, a couple of which were discussed in this earlier post.

On May 3, the jury issued a verdict with respect to asserted claims 37, 40 and 50 from the ‘372 patent, finding all of the claims invalid for obviousness and inadequate written description. The jury also found that none of the claims are literally infringed by Precision’s meganucleases, and that Precision is not liable for inducing or contributory infringement of the claims. The jury did find that Precision meganucleases infringe claims 37 and 50 under the doctrine of equivalents.

Here are the claims:

37. A recombinant monomer of an I-CreI meganuclease variant comprising at least one mutation in the amino acid sequence of SEQ ID NO: 70, wherein said at least one mutation comprises a substitution at one or more of the amino acids residues at positions 44, 68 and 70 and said monomer further comprises at least one additional mutation of an amino acid residue directly contacting a DNA target sequence wherein said amino acid residue directly contacting a DNA target sequence is selected from the group consisting of positions 26, 28, 30, 32, 33 and 38, wherein said monomer when in a dimeric form is able to cleave DNA.

40. The monomer of an I-CreI meganuclease variant of claim 37, wherein said monomer when in a dimeric form has a modified DNA cleavage specificity relative to the I-CreI meganuclease of SEQ ID NO: 70 in at least one nucleotide in the .+-.3 to 5 triplets.

50. A single-chain chimeric meganuclease comprising the fusion of two different monomers according to claim 37.

Earlier, on April 9, 2013, the District Court issued an order denying multiple motions on summary judgment, including one relating to literal infringement of Claim 40. In one interesting aspect of the decision, the District Court judge held that the term "variant of the wild-type monomer from 1-Crel"  (which appears in the preamble of claim 37, from which claim 40 depends) is an indefinite “limitation,” essentially because the court found that one of skill in the art would not be able to discern the breath of the term "variant." The court pointed out that the claim does not limit the number of mutations that could be present in the amino acid sequence of the claimed “variant,” and it is unclear at what point the number of mutations would cause the sequence to diverge so substantially from wild- type as to no longer constitute a "variant" of the wild type protein, but rather a distinct protein.  The use of this sort of open-ended "variant" language is not uncommon in patent claims of this type.

It will be interesting to follow this case if it is appealed to the Federal Circuit, particularly with respect to the issue of infringement under the doctrine of equivalents. The most important Federal Circuit precedent in this area of which I am aware comes from Genentech v. Wellcome, a 1994 decision in which the Federal Circuit reversed a jury's verdict which found a claim reciting tissue plasminogen activator (t-PA) infringed under the doctrine of equivalents by a substantially re-engineered, synthetic version of t-PA (marketed as a pharmaceutical). The allegedly infringing product differed substantially in structure from the claimed protein, with 15% fewer amino acids and 10-fold greater half-life. In a concurrence, Judge Lourie pointed out that while the traditional "function-way-result" test for infringement under the doctrine of equivalents might work well for some inventions, such as in the mechanical arts, it seems a poor fit for inventions like recombinant proteins.

 

 

 

Tuesday, April 16, 2013

Federal Circuit Affirms Decision Finding Biogen’s Patent Not Infringed by Arzerra



 Today in Biogen Idec v. GlaxoSmithKline a divided panel of the Federal Circuit affirmed a district court’s decision that GSK's monoclonal antibody product Arzerra does not infringe Biogen's patent number 7,682,612. I discussed the district court's decision in an October 2011 blog post. Arzerra is a fully human antibody that specifically binds to a small loop on the CD20 antigen. Biogen markets a competing product, Rituxan, which is a chimeric antibody that targets a different, larger loop on the CD20 antigen.
Representative claim 1 of Biogen's patent 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.
The dispute centered on the interpretation of the claim term "anti-CD20 antibody."  The District Court construed the term as limited to antibodies that bind to the same epitope of the CD20 antigen as Rituxan, i.e., the large loop. Under this interpretation, Biogen stipulated to noninfringement, since it is undisputed that Arzerra binds to a different epitope, i.e., the small loop.
On appeal, the Federal Circuit majority affirmed the district court's claim interpretation, based on the doctrine of "prosecution history disclaimer." The majority noted that while claim terms are generally given their ordinary and customary meaning, a "clear and unmistakable" disavowal of subject matter during prosecution overcomes the "heavy presumption" that claim terms carry their full ordinary and customary meaning. In this case, although the ordinary meaning of anti-CD20 antibody would presumably encompass any antibody that specifically recognizes any epitope on the CD20 antigen, the majority found that statements made during prosecution limited the claim to antibodies that bind at the same epitope as Rituxan. The majority pointed out that when representations are made by the time the during prosecution, "competitors are entitled to rely on those representations when determining a course of lawful conduct, such as launching a new product or designing-around a patented invention."
To summarize, during prosecution the examiner rejected Biogen’s claims for lack of enablement, finding that while the specification was enabling for Rituxan, but that it was "silent concerning what sort of specificity and affinity would be necessary" for other anti-CD20 antibodies. In response, Biogen pointed to its disclosure of Rituxan and argued that:
even 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.

After considering this argument, the examiner withdrew the enablement rejection. Even though the claims were not amended, the majority found that by arguing that the specification was enabling for antibodies with similar affinity and specificity as Rituxan, instead of challenging the examiner's understanding of the crucial terms, Biogen had effectively limited its claims to antibodies similar to Rituxan, i.e., antibodies binding the same epitope.
A dissenting opinion was filed by Judge Plager, who found that Biogen's arguments during prosecution were sufficiently ambiguous that they did not meet the "clear and unmistakable" disclaimer standard necessary to overcome the presumption that claim terms should be attributed their plain meaning. He voiced the opinion that Biogen's argument represented nothing more than "the give-and-take that is often part of the process of negotiation between it and examiner and an applicant [which] may result in less-than-clear understandings,” and that the majority had made "too much of such ambiguous statements."