Alnylam Pharmaceuticals is a biopharmaceutical company based in Cambridge, Massachusetts focused on developing synthetic "small interfering RNAs" (SiRNAs) as therapeutic agents. It has filed an amicus curiae brief in the Myriad gene patent case (AMP v. US PTO) that makes a number of insightful points, particularly in attempting to "debunk myths of Funk Brothers Seed Co. v. Kalo Inoculant Co."
Funk Brothers is generally assumed to be a case about patent eligibility. However, Alnylam points out that Funk Brothers was decided by the Supreme Court in 1948, prior to the enactment of the 1952 patent statute and thus prior to 35 USC 101, which is the statutory basis for the patent eligibility doctrine. Prior to 1952, the Court used the term “invention” to refer to "inventiveness," a concept that subsequent to 1952 and the enactment of 35 USC 103 we refer to as "nonobviousness." The Court in Funk Brothers found the claimed subject matter was not the “product of invention,” but Alnylam argues that post-1952 this statement should be interpreted a finding of obviousness, not patent ineligibility.
I have always found it extremely difficult, if not impossible, to find a principled distinction between the inventions claimed in Funk Brothers and Diamond V. Chakrabarty that would justify finding only Dr. Chakrabarty's invention patent eligible. In Funk Brothers, the alleged invention was a novel and useful combination, in a single inoculant, of naturally occurring microorganisms in a combination that did not exist naturally. Chakrabarty’s invention was a novel and useful combination, in a single microorganism, of naturally occurring plasmids in a combination that did not exist naturally. It is important to bear in mind that Chakrabarty's invention did not involve any genetic engineering at the molecular level.
In Funk Brothers, it has been pointed out that while the combination of bacteria in a single inoculant was novel, the bacteria function in the same manner and have the same characteristics as they would have in nature. But the same can be said regarding the plasmids Dr. Chakrabarty introduced into a single microorganism. These were naturally occurring plasmids, and in the claimed microorganism they encoded the exact same proteins, and performed the exact same function as they did in their natural state.
In a nutshell, Funk Brothers was a novel combination of naturally occurring bacteria capable of achieving novel and useful function, with the bacteria functioning in the same manner as they do in nature. Chakrabarty was a novel combination of naturally occurring plasmid DNA capable of achieving novel and useful function, with the plasmid DNA functioning in the same manner as they do in nature. I don't see how one invention can be patent eligible and the other not. However, if Funk Brothers was really decided based on obviousness rather than patent eligibility, as argued by Alnylam, the two decisions are easily reconciled.
Wednesday, November 10, 2010
Friday, November 5, 2010
Superficial Appeal of DOJ Brief Proves Illusory
I can understand why many people find the position advanced by the US government in AMP v. PTO (the DOJ amicus brief, discussed in an earlier post) quite appealing. On its face, it seems to offer a reasonable compromise: patent eligibility for "engineered" cDNA, but not for genomic DNA merely "excised" from a human chromosome. However, the distinction is superfical, and does not in my view withstand closer scrutiny.
In particular, the DOJ conveniently ignores the fact that in almost all cases isolation of genomic DNA involves amplification, either through laboratory techniques such as PCR, or by replication in recombinant cells. This distinguishes DNA and RNA from other biomolecules. Prior to the development of recombinant molecular biology in the 1970s, isolation of a naturally occurring biomolecule, such as a protein, involved removing the biomolecule produced in a naturally occurring from other biological constituents. Importantly, all of the purified biomolecule originated in the natural source, and was purified by separating it from other cellular constituents.
In contrast, because DNA can serve as a template for its own replication, DNA is normally isolated by amplifying it many times ("million-fold" is the term used in the amici brief filed by BIO and AUTM). As a result, a typical preparation of "isolated genomic DNA" actually consists primarily of synthetic copies of the genomic DNA molecule.
The DOJ makes much of the fact that a cDNA molecule does not contain the introns, which exist in most human genes, and implies that molecular biologists have "engineered" the introns out. In fact, the introns are naturally removed in the body when genomic DNA is transcribed into mRNA. There is no human engineering involved; production of a cDNA molecule simply entails making a DNA copy of a naturally occurring mRNA and then amplifying it.
In most instances a preparation of isolated genomic DNA comprises synthetic DNA molecules, produced in the laboratory by amplification, that correspond in sequence to a naturally occurring genomic DNA. A preparation of cDNA comprises synthetic DNA molecules, produced in the laboratory by amplification, that correspond in sequence to a naturally occurring mRNA. Considered in this light, I think that the distinction DOJ makes between "excised" genomic DNA versus "engineered" cDNA proves largely illusory.
True, a cDNA molecule has a slightly different chemical structure than the mRNA on which it is based, but the differences are small. The sugar group (ribose) in DNA is lacking an oxygen atom (hence the “deoxy”), and one of the four base groups in RNA (uracil) is slightly different than the corresponding base in DNA (thymine), due to replacement of a methyl group with a hydrogen atom. But mRNA and its corresponding cDNA both encode the same information, and both hybridize to the same complementary strand.
In many instances, a synthetic copy of a genomic DNA molecule is also chemically different from the original. Most naturally occurring genomic DNA is methylated, a form of epigenetic modification, while synthetic copies are often not methylated.
In short, the minor structural difference between cDNA and mRNA is not so qualitatively different than the difference between amplified genomic DNA and genomic DNA of natural origin to warrant using this distinction as the basis for drawing a line between patent eligible and patent ineligible subject matter.
In particular, the DOJ conveniently ignores the fact that in almost all cases isolation of genomic DNA involves amplification, either through laboratory techniques such as PCR, or by replication in recombinant cells. This distinguishes DNA and RNA from other biomolecules. Prior to the development of recombinant molecular biology in the 1970s, isolation of a naturally occurring biomolecule, such as a protein, involved removing the biomolecule produced in a naturally occurring from other biological constituents. Importantly, all of the purified biomolecule originated in the natural source, and was purified by separating it from other cellular constituents.
In contrast, because DNA can serve as a template for its own replication, DNA is normally isolated by amplifying it many times ("million-fold" is the term used in the amici brief filed by BIO and AUTM). As a result, a typical preparation of "isolated genomic DNA" actually consists primarily of synthetic copies of the genomic DNA molecule.
The DOJ makes much of the fact that a cDNA molecule does not contain the introns, which exist in most human genes, and implies that molecular biologists have "engineered" the introns out. In fact, the introns are naturally removed in the body when genomic DNA is transcribed into mRNA. There is no human engineering involved; production of a cDNA molecule simply entails making a DNA copy of a naturally occurring mRNA and then amplifying it.
In most instances a preparation of isolated genomic DNA comprises synthetic DNA molecules, produced in the laboratory by amplification, that correspond in sequence to a naturally occurring genomic DNA. A preparation of cDNA comprises synthetic DNA molecules, produced in the laboratory by amplification, that correspond in sequence to a naturally occurring mRNA. Considered in this light, I think that the distinction DOJ makes between "excised" genomic DNA versus "engineered" cDNA proves largely illusory.
True, a cDNA molecule has a slightly different chemical structure than the mRNA on which it is based, but the differences are small. The sugar group (ribose) in DNA is lacking an oxygen atom (hence the “deoxy”), and one of the four base groups in RNA (uracil) is slightly different than the corresponding base in DNA (thymine), due to replacement of a methyl group with a hydrogen atom. But mRNA and its corresponding cDNA both encode the same information, and both hybridize to the same complementary strand.
In many instances, a synthetic copy of a genomic DNA molecule is also chemically different from the original. Most naturally occurring genomic DNA is methylated, a form of epigenetic modification, while synthetic copies are often not methylated.
In short, the minor structural difference between cDNA and mRNA is not so qualitatively different than the difference between amplified genomic DNA and genomic DNA of natural origin to warrant using this distinction as the basis for drawing a line between patent eligible and patent ineligible subject matter.
Thursday, November 4, 2010
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.
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.
Monday, November 1, 2010
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).
Friday, October 29, 2010
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:
DOJ:
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.
Tuesday, October 26, 2010
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.
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.
Monday, October 25, 2010
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.
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