Myriad Genetics

On July 29, 2011, the Federal Circuit handed down its decision in Ass'n for Molecular Pathology et al. v. U.S.P.T.O., (often referred to as the “Myriad Genetics gene patent” case). The divided panel's three opinions reveal areas of broad agreement and notable disagreement about patent eligibility under 35 U.S.C. ' 101 of several categories of patent claims of interest to life sciences industries.

Background

The plaintiffs, an assortment of medical organizations, researchers, genetic counselors, and patients, brought suit against Myriad seeking a declaration that certain claims related to BRCA1 and BRCA2 (Breast Cancer Susceptibility Genes 1 and 2) were not patentable subject matter under 35 U.S.C. ' 101 and thus invalid. They challenged 15 composition and method claims from seven patents. The composition claims cover “isolated” human BRCA1 and BRCA2 genes and certain mutations associated with a predisposition to breast and ovarian cancers. A representative claim of this group recites “An isolated DNA coding for a BRCA1 polypeptide, said polypeptide having the amino acid sequence set forth in SEQ ID NO:2″ where SEQ ID NO:2 has the amino acid sequence of the BRCA1 protein. Other claims cover methods of “analyzing” or “comparing” a patient's BRCA sequence with the normal, or wild-type, sequence to identify the presence of cancer-predisposing mutations. One claim is directed to a method of screening potential cancer therapeutics by comparing the growth rates of cells containing a BRCA1 gene known to cause cancer both in, and outside, the presence of the potential therapeutic.

Granting the plaintiffs' motion for summary judgment of invalidity, the district court held: 1) that isolated DNA molecules fall within the judicially created “products of nature” exception to ' 101 because they are not “markedly different” from native DNAs; 2) the “analyzing” or “comparing” method claims were invalid under the (at the time definitive) “Machine or Transformation” test; and 3) the one method claim to “comparing” the growth rate of cells claimed a basic scientific principle and that the transformative steps were merely preparatory data gathering, and was thus invalid. The district court's opinion came as a surprise to many in the biotechnology industry who perceived it at odds with settled practice of what was patentable subject matter. Further increasing interest in the Federal Circuit's decision, the Solicitor General submitted an amicus brief advocating for a position different from what the PTO had been following for decades.

The Federal Circuit Reverses in Part

A divided Federal Circuit panel of judges Alan David Lourie (writing for the court), Kimberly Ann Moore (concurring), and William C. Bryson (dissenting in part): 1) reversed the district court's decision that the composition claims to “isolated” DNA molecules cover patent-ineligible products of nature; 2) reversed the decision that the method claim to screening potential cancer therapeutics via changes in cell growth was a patent-ineligible product of nature; and 3) affirmed the decision that the method claims directed to “comparing” or “analyzing” DNA sequences cover non-transformative abstract mental steps and are patent-ineligible.

Composition Claims to 'Isolated' DNA Molecules

Under the Supreme Court's Diamond v. Chakrabarty, 447 U.S. 303 (1980) and Funk Brothers Seed Co. v. Kalo Inoculant Co., 333 U.S. 127 (1948) decisions, the Federal Circuit found that the distinction between an unpatentable “product of nature” and a human-made invention for purposes of ' 101 turns on there being a change in the claimed composition's identity compared with what exists in nature. In particular, whether the composition has similar characteristics as in nature or whether human intervention has given it “markedly different,” or “distinctive,” characteristics. Applied to the isolated DNAs, the court concluded that the claimed molecules are “markedly different” ' have a different chemical identity and nature ' from the molecules that exist in nature. Reasoning that native DNA exists in the body as one of 46 large, contiguous DNA molecules (chromosomes), the court distinguished the claimed isolated DNA because “[i]solated DNA has been cleaved (i.e., had covalent bonds in its backbone chemically severed) or synthesized to consist of just a fraction of a naturally occurring DNA molecule.” Isolated BRCA1 and BRCA2, the court found, are not the DNA molecule as it exists in the body, but have been given a distinctive chemical identity through human intervention in cleaving or synthesizing a portion of a native chromosomal DNA. Prior cases addressed whether “purified” compositions were patent-eligible, and the court explained that, under its analysis, isolated DNAs are not “purified,” but are a molecule different from that in the body, and that those cases are inapplicable.

Judges Moore and Bryson, each writing separately, viewed the composition claims as falling into two sub-categories: those which claim complementary DNA (“cDNA”), and those which claim some portion of the genomic DNA for BRCA1/2. Both agreed the cDNA claims were patent-eligible because cDNA does not exist in nature ' normally it is synthesized in the lab, omits non-coding regions of DNA that exist in native DNA, and has a nucleotide sequence complementary to (and different from) the DNA for BRCA1/2. Myriad's claims which cover part or all of the full BRCA DNA sequence split the court, however. Judge Moore found that claims drawn to short sequences suitable for use as a probe or primer evidence an enlargement of the range of utility, and thus are patent-eligible. She also found claims to a DNA sequence that includes most or all of a gene to be patent-eligible out of policy concerns that Congress, not the judiciary, should alter the status quo in which they have been within the broad Congressional ambit of ' 101. Judge Bryson, in dissent, split from Judges Moore and Lourie, concluding the sub-category of isolated DNA is the same structurally and functionally as that in the native gene and thus such claims failed to meet requirements for patent-eligibility set forth in Chakrabarty and Funk Brothers.

Method Claims of 'Comparing' or 'Analyzing' Sequences

Several challenged claims recite a “method for screening a tumor sample,” by “comparing” a first BRCA1 sequence from a tumor sample and a second BRCA1 sequence from a non-tumor sample, where a difference in sequence indicates an alteration in the tumor sample. Unanimously, the court concluded that these claims fell outside ' 101 as reciting only abstract mental steps necessary to compare two different nucleotide sequences.

The Federal Circuit distinguished Prometheus Labs., Inc. v. Mayo Collaborative Servs., 628 F.3d 1347 (Fed. Cir. 2010), cert. granted 2011 WL 973139 (June 20, 2011)) (that currently is before the Supreme Court) which found “transformative,” and thus patent-eligible, a claim reciting “administering” a particular drug to a subject, and/or “determining” the drug's metabolites levels in the subject. Because Myriad's claims do not include “determining” the sequence of BRCA genes, e.g., by isolating the genes from a blood sample and sequencing them, they lacked a transformative step present in Prometheus.

Method of Screening Potential Cancer Therapeutics

The final challenged method involved: 1) “growing” host cells transformed with an altered BRCA1 gene in the presence or absence of a potential cancer therapeutic, 2) “determining” the growth rate of the host cells in the presence and absence of the potential therapeutic, and 3) “comparing” the growth rate of the host cells.

The court unanimously found such method claim patent-eligible. Under the “Machine or Transformation” test, the step of “growing” transformed host cells, in the presence or absence of a potential cancer therapeutic is inherently transformative. Because the claim does not cover all cells, compounds, or methods of determining therapeutic effect, it is not so “manifestly abstract” as to claim only a scientific principle.

Declaratory Judgment Jurisdiction

Myriad argued no plaintiff had sufficient standing to create declaratory judgment jurisdiction. The court found at least one did ' a physician to whom Myriad had directed a licensing letter in 1998 and who declared that he would immediately begin BRCA diagnostic testing if he were able to. Others who declared only that they would “consider” resuming testing were found to lack standing.

Implications

The implications of the decision are complex and not yet fully clear. Many view that a certiorari petition is likely; and guidance the decision provides for claiming within ' 101 may itself raise other concerns. In particular, the court's implicit suggestion of adding steps like “determining” the sequence at issue to methods similar to the “comparing” or “analyzing” claims may not be effective. Supreme Court review of Prometheus may alter the legal effect of that suggestion and doing so may mean that multiple actors, e.g., a treating clinician and unrelated analytical institution, would be required to directly infringe. The circumstances when either can be found to infringe is itself under en banc review in Akamai Techs., Inc. v. Limelight Networks, Inc., 629 F.3d 1311 (Fed. Cir. 2010), rehearing, en banc, granted, 2011 U.S. App. LEXIS 8167 (Fed. Cir. Apr. 20, 2011), and, while few predict that decision will change existing law radically, it is a nuanced, fact-intensive area that makes effective claim drafting a potential challenge.

For composition claims, the judges' rationales provide further guidance. Judge Lourie observed that “[g]enes are in fact materials having a chemical nature and, as such, are best described in patents by their structure rather than their function.” Judges Moore and Bryson both viewed “enlargement of the range of ' utility” as compared to nature significant in evaluating patent-eligibility. Judge Bryson's dissent elaborated his concern that the claims at issue covered sequence lengths beyond those which could provide the purported utility, e.g., as a probe or primer. Many practitioners draft specifications and claims with an eye to these issues currently, and additional attention may be warranted until the appeals run their course. The Federal Circuit's discussion distinguishing cases involving purified compositions may also warrant closer attention. Claims drawn to a purified polypeptide, purified human antibody, purified enzyme, etc. often are pursued and appear in many issued patents. The court's opinion distinguishes the isolated DNAs at issue from “purified” substance cases and raises for future cases the issue of whether ' 101 challenges will be made against such claims.

PTO practice also may be impacted. The government's (rejected) amicus position differs from long-standing PTO practice, and it remains to be seen how the PTO will implement the Myriad decision and incorporate conclusions the government reached in arriving at its position.

Furthermore, the progress of the field toward the promise of personalized medicine, common whole genome sequencing, and the evaluation of more complex interactions than those of a single gene mutation for diagnosis and therapy means that a host of issues for those pursuing patent protection in these areas are raised by the evolving law. Judicially created exceptions to patent subject matter may reduce the predictability that those investing research and development resources value, however. As Judge Moore observed, Congress' ability to investigate, canvass views and issues, and weigh competing interests may leave it better placed to define the boundaries of patentable subject matter. As the pressure from interested patients, clinicians, and the other constituencies appearing as plaintiffs indicates, and the more frequent-challenges the courts face applying the patchwork of judicially created exceptions to patentable subject matter reveals, it may be an area that Congress is asked to revisit.

Darren Donnelly is a partner in Fenwick & West LLP's litigation group specializing in patent litigation and counseling.

On July 29, 2011, the Federal Circuit handed down its decision in Ass'n for Molecular Pathology et al. v. U.S.P.T.O., (often referred to as the “Myriad Genetics gene patent” case). The divided panel's three opinions reveal areas of broad agreement and notable disagreement about patent eligibility under 35 U.S.C. ' 101 of several categories of patent claims of interest to life sciences industries.

Background

The plaintiffs, an assortment of medical organizations, researchers, genetic counselors, and patients, brought suit against Myriad seeking a declaration that certain claims related to BRCA1 and BRCA2 (Breast Cancer Susceptibility Genes 1 and 2) were not patentable subject matter under 35 U.S.C. ' 101 and thus invalid. They challenged 15 composition and method claims from seven patents. The composition claims cover “isolated” human BRCA1 and BRCA2 genes and certain mutations associated with a predisposition to breast and ovarian cancers. A representative claim of this group recites “An isolated DNA coding for a BRCA1 polypeptide, said polypeptide having the amino acid sequence set forth in SEQ ID NO:2″ where SEQ ID NO:2 has the amino acid sequence of the BRCA1 protein. Other claims cover methods of “analyzing” or “comparing” a patient's BRCA sequence with the normal, or wild-type, sequence to identify the presence of cancer-predisposing mutations. One claim is directed to a method of screening potential cancer therapeutics by comparing the growth rates of cells containing a BRCA1 gene known to cause cancer both in, and outside, the presence of the potential therapeutic.

Granting the plaintiffs' motion for summary judgment of invalidity, the district court held: 1) that isolated DNA molecules fall within the judicially created “products of nature” exception to ' 101 because they are not “markedly different” from native DNAs; 2) the “analyzing” or “comparing” method claims were invalid under the (at the time definitive) “Machine or Transformation” test; and 3) the one method claim to “comparing” the growth rate of cells claimed a basic scientific principle and that the transformative steps were merely preparatory data gathering, and was thus invalid. The district court's opinion came as a surprise to many in the biotechnology industry who perceived it at odds with settled practice of what was patentable subject matter. Further increasing interest in the Federal Circuit's decision, the Solicitor General submitted an amicus brief advocating for a position different from what the PTO had been following for decades.

The Federal Circuit Reverses in Part

A divided Federal Circuit panel of judges Alan David Lourie (writing for the court), Kimberly Ann Moore (concurring), and William C. Bryson (dissenting in part): 1) reversed the district court's decision that the composition claims to “isolated” DNA molecules cover patent-ineligible products of nature; 2) reversed the decision that the method claim to screening potential cancer therapeutics via changes in cell growth was a patent-ineligible product of nature; and 3) affirmed the decision that the method claims directed to “comparing” or “analyzing” DNA sequences cover non-transformative abstract mental steps and are patent-ineligible.

Composition Claims to 'Isolated' DNA Molecules

Under the Supreme Court's Diamond v. Chakrabarty , 447 U.S. 303 (1980) and Funk Brothers Seed Co. v. Kalo Inoculant Co. , 333 U.S. 127 (1948) decisions, the Federal Circuit found that the distinction between an unpatentable “product of nature” and a human-made invention for purposes of ' 101 turns on there being a change in the claimed composition's identity compared with what exists in nature. In particular, whether the composition has similar characteristics as in nature or whether human intervention has given it “markedly different,” or “distinctive,” characteristics. Applied to the isolated DNAs, the court concluded that the claimed molecules are “markedly different” ' have a different chemical identity and nature ' from the molecules that exist in nature. Reasoning that native DNA exists in the body as one of 46 large, contiguous DNA molecules (chromosomes), the court distinguished the claimed isolated DNA because “[i]solated DNA has been cleaved (i.e., had covalent bonds in its backbone chemically severed) or synthesized to consist of just a fraction of a naturally occurring DNA molecule.” Isolated BRCA1 and BRCA2, the court found, are not the DNA molecule as it exists in the body, but have been given a distinctive chemical identity through human intervention in cleaving or synthesizing a portion of a native chromosomal DNA. Prior cases addressed whether “purified” compositions were patent-eligible, and the court explained that, under its analysis, isolated DNAs are not “purified,” but are a molecule different from that in the body, and that those cases are inapplicable.

Judges Moore and Bryson, each writing separately, viewed the composition claims as falling into two sub-categories: those which claim complementary DNA (“cDNA”), and those which claim some portion of the genomic DNA for BRCA1/2. Both agreed the cDNA claims were patent-eligible because cDNA does not exist in nature ' normally it is synthesized in the lab, omits non-coding regions of DNA that exist in native DNA, and has a nucleotide sequence complementary to (and different from) the DNA for BRCA1/2. Myriad's claims which cover part or all of the full BRCA DNA sequence split the court, however. Judge Moore found that claims drawn to short sequences suitable for use as a probe or primer evidence an enlargement of the range of utility, and thus are patent-eligible. She also found claims to a DNA sequence that includes most or all of a gene to be patent-eligible out of policy concerns that Congress, not the judiciary, should alter the status quo in which they have been within the broad Congressional ambit of ' 101. Judge Bryson, in dissent, split from Judges Moore and Lourie, concluding the sub-category of isolated DNA is the same structurally and functionally as that in the native gene and thus such claims failed to meet requirements for patent-eligibility set forth in Chakrabarty and Funk Brothers.

Method Claims of 'Comparing' or 'Analyzing' Sequences

Several challenged claims recite a “method for screening a tumor sample,” by “comparing” a first BRCA1 sequence from a tumor sample and a second BRCA1 sequence from a non-tumor sample, where a difference in sequence indicates an alteration in the tumor sample. Unanimously, the court concluded that these claims fell outside ' 101 as reciting only abstract mental steps necessary to compare two different nucleotide sequences.

The Federal Circuit distinguished Prometheus Labs., Inc. v. Mayo Collaborative Servs. , 628 F.3d 1347 (Fed. Cir. 2010), cert. granted 2011 WL 973139 (June 20, 2011)) (that currently is before the Supreme Court) which found “transformative,” and thus patent-eligible, a claim reciting “administering” a particular drug to a subject, and/or “determining” the drug's metabolites levels in the subject. Because Myriad's claims do not include “determining” the sequence of BRCA genes, e.g., by isolating the genes from a blood sample and sequencing them, they lacked a transformative step present in Prometheus.

Method of Screening Potential Cancer Therapeutics

The final challenged method involved: 1) “growing” host cells transformed with an altered BRCA1 gene in the presence or absence of a potential cancer therapeutic, 2) “determining” the growth rate of the host cells in the presence and absence of the potential therapeutic, and 3) “comparing” the growth rate of the host cells.

The court unanimously found such method claim patent-eligible. Under the “Machine or Transformation” test, the step of “growing” transformed host cells, in the presence or absence of a potential cancer therapeutic is inherently transformative. Because the claim does not cover all cells, compounds, or methods of determining therapeutic effect, it is not so “manifestly abstract” as to claim only a scientific principle.

Declaratory Judgment Jurisdiction

Myriad argued no plaintiff had sufficient standing to create declaratory judgment jurisdiction. The court found at least one did ' a physician to whom Myriad had directed a licensing letter in 1998 and who declared that he would immediately begin BRCA diagnostic testing if he were able to. Others who declared only that they would “consider” resuming testing were found to lack standing.

Implications

The implications of the decision are complex and not yet fully clear. Many view that a certiorari petition is likely; and guidance the decision provides for claiming within ' 101 may itself raise other concerns. In particular, the court's implicit suggestion of adding steps like “determining” the sequence at issue to methods similar to the “comparing” or “analyzing” claims may not be effective. Supreme Court review of Prometheus may alter the legal effect of that suggestion and doing so may mean that multiple actors, e.g., a treating clinician and unrelated analytical institution, would be required to directly infringe. The circumstances when either can be found to infringe is itself under en banc review in Akamai Techs., Inc. v. Limelight Networks, Inc. , 629 F.3d 1311 (Fed. Cir. 2010), rehearing, en banc, granted, 2011 U.S. App. LEXIS 8167 (Fed. Cir. Apr. 20, 2011), and, while few predict that decision will change existing law radically, it is a nuanced, fact-intensive area that makes effective claim drafting a potential challenge.

For composition claims, the judges' rationales provide further guidance. Judge Lourie observed that “[g]enes are in fact materials having a chemical nature and, as such, are best described in patents by their structure rather than their function.” Judges Moore and Bryson both viewed “enlargement of the range of ' utility” as compared to nature significant in evaluating patent-eligibility. Judge Bryson's dissent elaborated his concern that the claims at issue covered sequence lengths beyond those which could provide the purported utility, e.g., as a probe or primer. Many practitioners draft specifications and claims with an eye to these issues currently, and additional attention may be warranted until the appeals run their course. The Federal Circuit's discussion distinguishing cases involving purified compositions may also warrant closer attention. Claims drawn to a purified polypeptide, purified human antibody, purified enzyme, etc. often are pursued and appear in many issued patents. The court's opinion distinguishes the isolated DNAs at issue from “purified” substance cases and raises for future cases the issue of whether ' 101 challenges will be made against such claims.

PTO practice also may be impacted. The government's (rejected) amicus position differs from long-standing PTO practice, and it remains to be seen how the PTO will implement the Myriad decision and incorporate conclusions the government reached in arriving at its position.

Furthermore, the progress of the field toward the promise of personalized medicine, common whole genome sequencing, and the evaluation of more complex interactions than those of a single gene mutation for diagnosis and therapy means that a host of issues for those pursuing patent protection in these areas are raised by the evolving law. Judicially created exceptions to patent subject matter may reduce the predictability that those investing research and development resources value, however. As Judge Moore observed, Congress' ability to investigate, canvass views and issues, and weigh competing interests may leave it better placed to define the boundaries of patentable subject matter. As the pressure from interested patients, clinicians, and the other constituencies appearing as plaintiffs indicates, and the more frequent-challenges the courts face applying the patchwork of judicially created exceptions to patentable subject matter reveals, it may be an area that Congress is asked to revisit.

Darren Donnelly is a partner in Fenwick & West LLP's litigation group specializing in patent litigation and counseling.