Summary of Myriad Patent Claims Under Attack in AMP v. PTO

Today I published a short article in Managing IP "discerning" Myriad's patent claims, currently under attack in AMP v. PTO . The article is available here for subscribers to Managing IP, along with other materials relating to the Myriad case.

The substance of my article is as follows:

As a preliminary matter, it bears noting that the precise contours of Myriad's patent claims are not entirely clear. Claim interpretation is a notoriously unpredictable exercise, and no court has ever formally construed the claims, or considered their scope in the context of infringement litigation. In fact, no US court has ever interpreted a human gene patent claim in a case involving genetic diagnostic testing. In an amicus brief filed with the Federal Circuit in AMP v. PTO, the author (Holman) and Robert Cook-Deegan explain that if the claims were ever enforced in an infringement suit there are reasons to believe that the claims would not be interpreted as broadly as many critics of gene patents have assumed. The following analysis is based on a facial reading of the claims in view of the patent specifications, as well as statements made by the district court and by Myriad.

The challenged patent claims recite subject matter falling under general three categories: isolated DNA molecules claimed as compositions of matter, methods of diagnostic testing, and cell-based assay methods. Importantly, none of the claims encompass DNA as it exists naturally in the human body, and none of the claims recite mere genetic information. Thus, popular allegations that the patent claims confer ownership on people's bodies, or can be used to prevent a doctor from communicating the existence of a genetic predisposition to cancer to a patient, would appear to be unfounded.

Isolated DNA claims
All of the composition of matter claims are limited to "isolated" DNA molecules, and hence clearly do not encompass genomic DNA as it exists naturally in the human body. This is consistent with long-standing patent office policy which requires claims directed to naturally occurring DNA molecules to be limited to isolated, purified and/or recombinant embodiments of the molecule, in order to prevent the patent from covering native genes in the human body

There is, however, some uncertainty with respect to exactly how broadly the term "isolated" should be interpreted. Myriad's patent specifications define the term to encompass any DNA sequence that has been “removed from its naturally occurring environment, and includes recombinant or cloned DNA isolates and chemically synthesized analogs or analog biologic synthesized by heterologous systems." Many in the biotechnology community have assumed that claims to "isolated" DNA molecules broadly encompass the claimed sequence in any context outside its native environment, such as residing in a recombinant DNA vector, cell or organism. However, there is little US case law directly addressing the proper interpretation of the term "isolated" in this context, and there is reason to believe that if litigated the term might be given a narrower construction, at least in some cases (depending, for example, on how the term "isolated" is used in the patent specification and in communications to the patent office during patent prosecution).

Some of the composition of matter claims encompass any isolated DNA that codes for a full length BRCA1 or BRCA2 protein. These claims are relatively broad in the sense that they would appear to cover any of the astronomical number of redundant DNA sequences that would encode the BRCA1 protein. They also arguably cover genomic DNA coding for the protein, i.e., the isolated gene as it exists in the human body. Assuming the courts gives the term "isolated" an expansive reading, the claims arguably cover very large recombinant molecules that comprise the BRCA coding sequence (i.e., large DNA vectors), as well as recombinant cells or organisms comprising the coding sequence in a non-native context.

Although many have assumed that claims directed towards DNA encoding full-length BRCA proteins can be used to block genetic diagnostic testing, in fact these claims would not appear to be infringed by standard genetic diagnostic testing. In conventional BRCA diagnostic testing, segments of the BRCA gene are amplified and sequenced, not the entire full-length genomic sequence. As a consequence, the full-length coding sequence is not made or used, and thus there would seem to be no infringement (see Holman/Cook-Deegan amici brief). The claim would however appear to cover a recombinant DNA molecule encoding a full-length BRCA protein, which could be used in drug discovery research or, potentially, gene-based therapy.

There are also a variety of narrower isolated DNA claims at issue. For example, some of the isolated DNA claims are limited to a specific cDNA molecule encoding a BRCA protein. These claims are relatively narrow, and could be readily circumvented in many instances by simply using a different DNA sequence that encodes the same protein (which is trivial given the redundancy of the genetic code and the general availability of whole gene synthesis). Although the district court found the cDNA claims patent ineligible, the government argues in its amicus brief that while isolated genomic DNA is patent ineligible, cDNA is patent eligible because it does not exist in nature (cDNA is essentially a DNA version of a naturally existing RNA molecule).

Some of the claims recite any isolated DNA having least 15 nucleotides of a DNA sequence encoding full-length BRCA protein. These claims appear on their face to be extremely broad, encompassing conventional BRCA genetic diagnostic testing (because the testing involves amplification of fragments of the BRCA gene exceeding 15 nucleotides in length). However, a recent bioinformatics study suggests that the breadth of these claims could render them invalid based on anticipation by genetic sequences published in GenBank more than one year before the patents’ filing dates (see Holman/Cook-Deegan amici brief).

Method of diagnosis claims
The method of diagnosis claims are generally directed towards processes of "analyzing" a person's BRCA gene sequence for the existence of a naturally occurring mutation or genetic variation, or “comparing” two BRCA sequences in order to identify the existence of a variation. Critics of gene patents have argued that these method claims broadly cover the mere mental process of analyzing or comparing genetic sequence information, and this was the interpretation of the district court in its summary judgment opinion. However, in their appellant brief Myriad argues for a narrower interpretation, explaining that when the claims are read in light of the specification it is clear that the claims require "extracting, processing and analyzing” DNA molecules, not merely an analysis or comparison of genetic information.

The scope of these method claims could be significant. For example, in the not-too-distant future it is predicted that many people will have their whole genome sequenced. With this information in hand, one could then look for medically significant genetic variations, such as variations in the BRCA gene. Under the district court's broad interpretation, the method claims might be infringed by a doctor or patient merely analyzing the genetic information, which is one of the fears voiced by critics of gene patents. On the other hand, under Myriad's proposed interpretation merely analyzing genetic information would not constitute infringement.

Cell-based assay methods
One of the challenged patent claims recite a method of using recombinant cells engineered to express a BRCA protein to screen for potential cancer drugs. This claim clearly has no implications for genetic testing, and it is unclear why the ACLU chose to challenge its patent eligibility.

Links to Holman/Cook-Deegan and DOJ Amicus Briefs Are Now Operational (I think)

On Friday I thought I posted links to amicus briefs filed by Holman/Cook-Deegan and DOJ in AMP v. PTO, but turns out they were not operational, I believe the problem has been corrected. Just in case, the link to Holman/Cook-Deegan brief is here. Please let me know if still not working (they work on my computer).

Two Amicus Briefs Filed in ACLU Gene Patent Case: Holman/Cook-Deegan and DOJ

Robert Cook-Deegan and I just submitted an amicus brief in AMP v. PTO, the ACLU challenge to Myriad's gene patents, available here. The brief was filed on behalf of neither party, but we ask the court to reverse the district court on its determination that the claims at issue are patent ineligible.

Robert Cook-Deegan directs the Center for Public Genomics, Duke University, which conducted eight case studies of the impact of patenting and licensing on genetic testing for ten clinical conditions commissioned by the US Secretary’s Advisory Committee for Genetics, Health and Society, published in April 2010.


A brief submitted by the DOJ on behalf of neither party is available here.


DOJ asks the court to reverse the district court’s invalidation of the composition claims that are limited to cDNAs and similar man-made constructs, but affirm the district court’s conclusion that the claims encompassing isolated human genomic DNA are invalid.


Here are Summaries of the Arguments:

Holman/Cook-Deegan:

In their zeal to address perceived public policy concerns associated with
Myriad’s gene patents, and more particularly Myriad’s controversial business and
patent enforcement practices, plaintiffs have invoked the recently re-invigorated
patent eligibility doctrine in a manner that threatens to wreak substantial collateral
damage on future innovation in genetic diagnostic testing, personalized medicine,
and biotechnology in general. DNA patents have created incentives critical in
attracting the substantial investment necessary to fuel the discovery and
development of life-saving products produced by the biotechnology industry.
Although plaintiffs have identified numerous potential concerns with gene patents
in the context of some types of genetic diagnostic testing, to date there is
insufficient evidence that harms attributable to patents on genes justify broad,
subject matter-based invalidation of all patents made of or based on DNA. More
appropriate and targeted legal and policy solutions to problems associated with
some gene patents and patent enforcement practices are preferable to the blunt
doctrinal instrument of patent eligibility. The decision below should be reversed in
order to prevent substantial unintended negative consequences for innovation in
this increasingly important technology sector, and to enable adjudication of
patentability using other tools that are more appropriate to the task

.


DOJ:

Section 101 marks the “threshold” of the patent system. Bilski v.
Kappos, 130 S.Ct. 3218, 3225 (2010). It not only “defines the subject
matter that may be patented,” ibid., but simultaneously defines what
must remain in “‘the storehouse of knowledge of all men * * * free to all
men and reserved exclusively to none,’” ibid. (quoting Funk Brothers
Seed Co. v. Kalo Inoculant Co., 333 U.S. 127, 130 (1948)); see Bonito
Boats, Inc. v. Thundercraft Boats, Inc., 489 U.S. 141, 151 (1989) (the
patent laws “determine not only what is protected, but also what is free
for all to use”). The boundary between eligible and non-eligible subject
matter is defined, in significant part, by the settled principle that the
patent laws do not embrace laws of nature, physical phenomena, or
abstract ideas. See Bilski, 130 S.Ct. at 3225.
In attempting to apply that principle here, the district court
erroneously cast doubt on the patent-eligibility of a broad range of manmade
compositions of matter whose value derives from the informationencoding
capacity of DNA. Such compositions — e.g., cDNAs, vectors,
recombinant plasmids, and chimeric proteins, as well as countless
industrial products, such as vaccines and genetically modified crops,
created with the aid of such molecules — are in every meaningful sense
the fruits of human ingenuity and thus qualify as “‘human-made
inventions’” eligible for patent protection under section 101. J.E.M. Ag
Supply, Inc. v. Pioneer Hi-Bred Int’l, Inc., 534 U.S. 124, 130 (2001)
(quoting Diamond v. Chakrabarty, 447 U.S. 303, 313 (1980)). The
district court therefore erred in invalidating the challenged composition
claims, such as claim 2 of the ‘282 patent, that are directed solely to
cDNAs.
The district court correctly held, however, that genomic DNA that
has merely been isolated from the human body, without further
alteration or manipulation, is not patent-eligible. Unlike the
genetically engineered microorganism in Chakrabarty, the unique
chain of chemical base pairs that induces a human cell to express a
BRCA protein is not a “human-made invention.” Nor is the fact that
particular natural mutations in that unique chain increase a woman’s
chance of contracting breast or ovarian cancer. Indeed, the relationship
between a naturally occurring nucleotide sequence and the molecule it
expresses in a human cell — that is, the relationship between genotype
and phenotype — is simply a law of nature. The chemical structure of
native human genes is a product of nature, and it is no less a product of
nature when that structure is “isolated” from its natural environment
than are cotton fibers that have been separated from cotton seeds or
coal that has been extracted from the earth.
The scope of Section 101 is purposefully wide and its threshold is
not difficult to cross. See Bilski, 130 S.Ct. at 3225. New and useful
methods of identifying, isolating, extracting, or using genes and genetic
information may be patented (subject to the prohibition against
patenting abstract ideas), as may nearly any man-made transformation
or manipulation of the raw materials of the genome, such as cDNAs.
Thus, the patent laws embrace gene replacement therapies, engineered
biologic drugs, methods of modifying the properties of plants or
generating biofuels, and similar advanced applications of biotechnology.
Crossing the threshold of section 101, however, requires something
more than identifying and isolating what has always existed in nature,
no matter how difficult or useful that discovery may be.

The ACLU Gene Patent Challenge: Analysis of Myriad's Brief

Yesterday I posted a link to the brief filed last Friday by Myriad Genetics with the Federal Circuit in the case of AMP v. PTO (ACLU and Public Patent Foundation challenge to gene patents). In their brief, Myriad argues that (1) the district court should have dismissed the case for lack of jurisdiction, because there was no evidence of any real or immediate dispute between Myriad in any plaintiff; (2) composition of matter claims directed towards isolated DNA molecules are patent eligible, in part because they have "markedly different characteristics" than their naturally occurring counterparts; and (3) method of diagnosis claims are patent eligible, in part because they all require physical transformation of a DNA sample (i.e., isolation, processing and analysis) that satisfies the Bilski machine-or-transformation test.

Lack of Jurisdiction

Myriad argues that the 20 plaintiffs were all recruited by the ACLU and Public Patent Foundation (referred to herein collectively as ACLU) in order to further those group’s agenda of abolishing gene patents, and that there is no evidence of any current dispute between Myriad and any of the plaintiffs. According to Myriad, only three of the plaintiffs have ever been contacted by Myriad, and those three were contacted more than a decade before the filing of the complaint. Myriad argues that none of the plaintiffs has a controversy "of sufficient immediacy and reality to warrant the issuance of a declaratory judgment" under the MedImmune standard.


Composition of Matter Claims

Myriad begins by arguing that the district court was incorrect in its conclusion that "products of nature" are patent ineligible, pointing out that such a "sweeping exception" would bar the patenting of important inventions like pharmaceuticals derived from natural sources (e.g., Taxol), and would be inconsistent with cases finding isolated natural products patentable that date back nearly 100 years.

Myriad goes on to argue that even if the district court is correct, and isolated products of nature are only patent eligible if they display "markedly different characteristics" compared to the product as exists in nature, Myriad's isolated BRCA gene sequences clearly satisfy the test. Myriad points out that it is inconsistent for plaintiffs to argue on the one hand that the claimed isolated BRCA molecules are necessary for performing BRCA diagnostic testing, while at the same time arguing that the claimed isolated molecules have no "markedly different characteristics" from their naturally occurring counterparts. They note that native DNA is useless for the diagnostic and detection applications for which the isolated molecules must be utilized.

Myriad addresses the much discussed dissent by Judge Dyk in his separate opinion in Intervet, which many have interpreted as signaling his skepticism with respect to the patent eligibility of isolated gene sequences. In his opinion, Judge Dyk suggested that it "would be difficult to argue, for instance, that one could patent a leave of a plant merely because the leaves do not occur in nature in an isolated form." Myriad points out that not only would Judge Dyk’s hypothetical leave likely fail under sections 102 and 103 for lack of novelty and obviousness, it would fail the "markedly different characteristics" test "because the plucked leaf would have exactly the same properties as the unplucked leaf-unlike here, where isolated DNA molecules possess significantly different structural and functional characteristics from native DNA."


Method Claims

Critics of Myriad's gene patents have complained that the claims are much too broad, claiming the information content of the BRCA genes, and totally precluding doctors and patients from looking at or discussing the presence of genetic variations in the BRCA genes. For example, some of the challenged method claims could be interpreted broadly to cover comparing a patient's BRCA sequence with wild-type BRCA in order to identify genetic variations (which could be clinically significant).
However, in their brief Myriad argues for a narrower interpretation, under which all the method claims could only be infringed by a party that isolates and analyzes DNA molecules (as opposed to genetic sequence information). This could be a significant limitation that avoids some of the fears that have been raised with respect to the inability to design around these patent claims. For example, I am reading a book called The $1000 Genome, by Kevin Davies, which describes new technology that is rapidly coming online which will enable people to inexpensively determine the sequence of their entire genome. Salzberg and Pertea recently published an article in Genome Biology called "Do-It-Yourself Genetic Testing,” (described recently on the Patent Docs blog), which purports to allow a person who knows her BRCA sequences to analyze for variations predictive of cancer. It seems to me that in the not-too-distant future method claims such as Myriad’s could be readily circumvented by having one's whole genome sequenced (without asking the sequencer to analyze for BRCA mutations), and then using a computational screen such as the one provided by Salzberg and Pertea to analyze for clinically relevant variations.

Myriad argues that because its method claims all require isolation and processing of DNA molecules, they satisfy the transformation prong of Bilski's machine or transformation test. They correctly note that the Federal Circuit's Prometheus decision explicitly held that diagnostic methods that involve processing a biological sample "necessarily involve a transformation,” and thus pass the machine or transformation test. The Supreme Court in Bilski v. Kappos clarified that the machine or transformation test is not the exclusive test for patent eligibility, but acknowledged that in most instances the existence of a machine or transformation is highly relevant to the question of patent eligibility. The Supreme Court vacated the Federal Circuit's original Prometheus decision, and remanded for the Federal Circuit to reconsider in light of Bilski v. Kappos. I predict that when the Federal Circuit issues a new decision in Prometheus, it will maintain the holding that diagnostic methods involving physical manipulation of biological samples are transformative and generally patent eligible.

Myriad goes on to point out that Bilski v. Kappos "remove any suggestion that the rigid 'machine-or-transformation' test provides the exclusive test for patent eligibility, particularly as applied to "Information Age" technologies like the advanced diagnostic techniques claimed injury and patents." In contrast with the method of hedging claims found to be unpatentable abstract ideas in Bilski, Myriad argues that its methods represent "very real ways of diagnosing and treating cancers."
Interestingly, Myriad does not address the question of whether its method claims impermissibly encompass a natural phenomenon. Supreme Court precedent makes clear that natural phenomena are patent ineligible, and prior to the Federal Circuit's In re Bilski decision most patent eligibility challenges to biological method claims (particularly diagnostic claims) focused on arguments that the method claim preempted the practical use of a natural phenomenon. I have discussed this often on this blog, particularly with respect to the Prometheus and Classen cases, and Justice Breyer's often cited dissent from LabCorp.

Predictions?

I don't have a good sense as to how the Federal Circuit will decide the issue of jurisdiction, it seems to me that the threat of being sued for patent infringement was nonexistent for many of the plaintiffs, and highly speculative for others.

However, I do think that if the Federal Circuit finds jurisdiction it will uphold the validity of isolated polynucleotide claims and methods of diagnosis claims, so long as those method claims require the performance of physically transformative processes (isolation, processing and analysis of molecules).

On the other hand, a broad method claim that could be infringed by the mere analysis of genetic information, without requiring any physically transformative step, would I think face a significant threat of invalidation for patent eligibility under Bilski. I suspect this is why Myriad is arguing for a narrower interpretation.

Myriad Files Brief in AMP v. PTO

Myriad filed its brief with the Federal Circuit last Friday in its appeal of the district court decision in AMP v. PTO, which found Myriad's gene patents to be patent ineligible. The brief is available here, I will provide some commentary tomorrow.

Yeda Appeals Board Decision Favoring Abbott in TBP-II Interference

Abbott and the Yeda Research and Development Co. have been involved in a patent interference since 1996 over the right to patent TNF-alpha Binding Protein II (TBP-II, also known as TNF receptor 2). This is a therapeutically and commercially relevant protein. ENBREL (etanercept), a biologic drug developed and marketed by Immunex (now Amgen) for the treatment of autoimmune disease, is a fusion protein comprising the Fc component of human immunoglobulin G1 and TBP-II. I don't know what the specific commercial implications of the patent interference are, but clearly the parties view the patent as sufficiently valuable to justify the cost of a prolonged interference contest. A corresponding patent application claiming the genetic sequence encoding TBP-II was the subject of an important 2004 Federal Circuit decision relating to the written description requirement (In re Wallach).

The interference involves a patent issued to Abbott (5,344,915) and Yeda’s US patent application. The inventor on the Yeda application is Wallach (claiming common priority to the application at issue in In re Wallach). The interference was declared by the patent office in 1996, and resulted in a "Final Decision" by the Board of Patent Appeals and Interferences (the Board). In this decision, the Board invalidated Abbott's patent as anticipated by a prior art reference. Abbott claimed priority to two German applications that would have predated the invalidating prior art reference, but the Board denied Abbott the benefit of these two earlier filing dates. The Board essentially held that the German applications did not satisfy the written description requirement of section 112 with respect to the claimed invention.

The German applications disclosed an isolated protein, defined in terms of its approximate molecular weight and an incomplete N-terminal sequence. The applications also disclosed the source of the protein (the urine of patients with fever) and the method used to purify the protein. Abbott's US patent claims the protein as a "purified and isolated TNF-alpha binding protein which has a molecular weight of about 42,000 daltons and has at the end terminus the amino acid sequence [the specific amino acid sequence of the N-terminus of TBP-II]” The critical difference between the patent claims and the disclosure in the German applications is the N-terminal amino acid sequence. In the German applications, there was some uncertainty about the exact N-terminal sequence, and some amino acids in the sequence were not disclosed. These ambiguities were addressed and resolved in the subsequent filed US patent.

The Board’s decision was based on its determination that the earlier incomplete disclosure failed to adequately describe the more complete amino acid sequence provided in the ultimately issued claims. Abbott argued that the proteins described in the US patent claims and the German applications are the same, as demonstrated by the fact that they have the same molecular weight, bind specifically to TNF-alpha, are isolated from the same source (urine from patients with fever), and isolated and purified using the same methods. In essence, Abbott argued that the German applications inherently disclosed the later claimed protein. However, the Board rejected this argument, finding that the record failed to establish to the necessary degree of certainty that TBP-II was inherently disclosed in the German applications, and noting that "inherency may not be established by probabilities or possibilities."

Abbott appealed the Board decision under 35 USC 146 to the District Court for the District of Columbia. In 2008 the District Court granted Abbott's motion for summary judgment, vacated the Board's final decision and remanded to the Board for further proceedings. The District Court was obliged to review the Board's decision under the "clearly erroneous" standard, but even under this deferential standard of review the court reversed the Board, holding that the German applications inherently disclosed the later claimed protein to a degree of certainty sufficient to satisfy the written description requirement. The court rejected alleged ambiguities raised by Yeda (and accepted by the Board) with respect to the identity of the protein disclosed in the German applications.

Yeda appealed the district court decision to the Federal Circuit, but in 2009 the court dismissed the appeal, holding that they did not have jurisdiction to hear the case prior to a final decision in the interference.

On remand, the Board granted Abbott priority benefit of the German applications, and in May 2010 awarded judgment in the interference to Abbott.

On September 9, 2010, Yeda filed its appeal under 35 USC 146, again in the District of Columbia, challenging the Board's decision. It seems likely the case will continue on for at least several more years, since the District Court's decision will begin be subject to appeal to the Federal Circuit (which should have jurisdiction to hear the case since a final decision will have been rendered in interference).

It interesting to compare this case with Goeddel v. Sugano, a September 7 Federal Circuit decision regarding a patent interference over mature human fibroblast interferon (beta interferon). At issue were claims directed to the mature form of the protein, and the DNA encoding the mature form of the protein.

The mature form of fibroblast interferon is produced by cleaving a 21 amino acid presequence from the N-terminal of precursor fibroblast interferon. Sugano attempted to claim priority to a Japanese application that disclosed the full length precursor protein, and also disclosed the N-terminal sequence of the mature protein. Based on this disclosure, clearly anyone that knows anything about molecular biology would know the sequence of the mature protein - it is simply the portion of the disclosed precursor protein sequence that begins with the N-terminal sequence of mature protein.

However, whoever drafted Sugano’s Japanese patent application (filed more than 30 years ago) apparently did not see the need to point out the obvious, and thus there is no explicit disclosure in the application specifically pointing out the sequence of the mature protein. Because the Japanese application failed to connect the dots, the Federal Circuit held that the Japanese patent application did not satisfy the requirements of section 112 first paragraph (enablement and/or written description), and as a result awarded priority to Goedell.

It seems to me a good argument could be made that the Sugano Japanese application inherently but unambiguously disclosed the sequence of the mature protein. This strict application of the written description requirement is arguably inconsistent with the relatively lenient standard applied by the District Court in reversing the first Board decision in the interference involving Abbott and Yeda.

I say arguably, because even though both interferences involve claims directed to proteins, the facts are quite distinct. In Yeda v. Abbott, the court found that the claimed protein was the same protein disclosed in the priority applications, even though the earlier disclosure provided less detail with respect to the amino acid sequence of the protein. In Goeddel v. Sugano, on the other hand, the priority document provided the full amino acid sequence of the later claimed protein, but failed to explicitly point out the distinction between the mature protein and the precursor protein from which it is derived.

Glaxo Fires Latest Shot in Patent Battle with Genentech over Therapeutic Molecule Antibodies

On September 20, Glaxo Smith Kline (Glaxo) sued Genentech for infringement of US patent numbers RE40,070 and RE41,555 in the District of Delaware. The patents claim methods of purifying monomeric IgG antibody using hydrophobic interaction chromatography. GSK alleges in its complaint that Genentech's production of therapeutic monoclonal antibody products, specifically Herceptin, infringes the patents. Herceptin is an important monoclonal antibody therapeutic used to treat HER2 positive breast cancer. The complaint is available here.

The lawsuit is the latest volley in an ongoing patent war between GSK and Genentech over recombinant monoclonal antibody technology. Most of the patents that have been asserted are directed towards general methodologies used in the production and formulation of monoclonal antibody therapeutics.

For example, in 1999 Glaxo sued Genentech for allegedly infringing US patent numbers 5,545,403 and 5,545,405 (both generally claiming methods of treatment using recombinant antibody glycosylated by Chinese hamster ovary (CHO) cells), and US patent numbers 5,654,403 and 5,792,838 (both directed towards methods of stabilizing antibody formulations using copper chelators). Glaxo alleged that the patents were infringed by Genentech's production of Herceptin and Rituxan, two cancer drugs that target breast cancer whose tumors over express the HER2 protein and CD20 positive, B-cell non-Hodgkin's lymphoma, respectively. A district court held for Genentech, finding all of the asserted Glaxo claims invalid and/or not infringed. The case settled while on appeal to the Federal Circuit.

In 2000, Glaxo sued Genentech for allegedly infringing US patent number 5,633,162, which claims methods of growing CHO cells in a serum-free medium. While the complaint does not specifically identify the allegedly infringing Genentech products, Genentech reported in a filing to SEC that it assumed that the lawsuit was directed towards Herceptin and Rituxan. This case settled early in the litigation.

In 2009, Glaxo received FDA approval to market Arzerra, an anti-CD20 approved for the same indication as Genentech's Rituxan (chronic lymphocytic leukemia). Thus, the two products can be viewed as direct market competitors, perhaps biosimilars (we are still awaiting guidance from FDA as to criteria for biosimilarity under the new biosimilarity legislation passed by Congress as part of healthcare reform).

In 2009, Glaxo filed a declaratory judgment action in the Southern District of Florida seeking a judgment of invalidity, unenforceability and noninfringement with respect to Genentech's patent number 6,331,415. This patent is widely referred to as the “Cabilly II” patent, and came out of a highly publicized interference between Genentech and Celltech. The patent broadly covers the co-expression of immunoglobulin heavy and light genes in a single host cell. Genentech has been quoted as stating that the patent is "the backbone of recombinant antibody production in the biotech industry." Genentech has already asserted the patent against MedImmune and Centocor, alleging that those companies’ production of monoclonal antibodies products Synagis, ReoPro and Remicade infringe the patent. The litigation between Genentech and MedImmune resulted in a Supreme Court decision on standing of a patent licensee to bring a declaratory judgment action action challenging the patent. Genentech successfully moved to have the litigation transfer to the Central District of California, where the Centocor and MedImmune litigations are located.

In 2010, Genentech (along with Biogen Idec, its partner in the marketing of Rituxan) sued Glaxo in the Southern District of California for allegedly infringing US patent number 7,682,612. The patent claims methods of treating chronic lymphocytic leukemia using an anti-CD20 antibody, and thus invalid would appear on its face to be infringed by Arzerra. This case is somewhat noteworthy, since it is the only one in which the patent is specifically directed towards an antibody recognizing a specific antigen (CD20), as opposed to the other patents all relating to general methods of antibody production and formulation.