AMP v. USPTO: Myriad wins this battle, but will the war continue?
| August 16, 2011
Association for Molecular Pathology v. USPTO (CAFC 2011)
2011年7月29日、CAFCはAMP v. USPTO（Myriadは上訴人としてUSPTO側に名を連ねる）、地裁のSweet判事の判決（単離DNA配列は特許対象ではない）を棄却し、DNAクレームは特許保護適格があると判断した。
単離DNAクレームに関する多数意見
被控訴人（特許反対派）は、単離されたDNAと自然界のDNAはいずれも同じ遺伝子情報を持つものであり、それらは「著しく異なる」ものではないと主張した。CAFCの多数意見はこれを受け入れず、「単離されたDNAが、自然物と類似する情報的性質を持っているという理由で、その特許対象適格性が否定されることはない」と述べた。多数意見は、単離精製されたリチウム元素、地中から発掘されたダイヤモンド、木から採取した葉など様々なアナロジーを用いて議論した。最終的に多数意見は、単離DNAは「天然DNAと著しく異なる化学的性質（つまり化学的相違）がある」という議論に戻って、単離DNAは特許可能な主題であると結論づけた。さらに、このような主題を特許対象から除外するには米国議会の判断が必要であると付け加えた。
この事件の異色な一面であるが、米司法省が意見を述べている。米国政府は、特許対象適格のテストとして「マジックマイクロスコープ」テストを適用すべきであると主張した。つまり、完全に同一の配列が自然界に見い出されるのであれば、特許すべきではないが、そのような完全同一の配列が見い出されなければ特許してもよい、というテストである。これに対しLourie判事は、それが目に映るからといって、特定のDNAが切断されて単離されるわけではなく、このような行為は人間の発明行為であると述べ、反対した。
単離DNAクレームに関するMoore判事の意見
Moore判事はまず、cDNAはイントロンが除去されており、自然界には存在しないという理由で特許可能であるとした。他方、自然界の配列と同一のDNA配列についても多数意見に同意しているが、短鎖DNA断片については、「有用性の範囲の拡大」という理由を付け加えた。Moore判事は、自然状態のDNA断片は診断に使用され得るものではないことを指摘し、単離されたDNA断片は「もともと自然界に属する事象の一端」として機能するものではなく、自然界に存在する場合とは「異なる有益な有用性」があると述べた。
しかし、Moore判事は、遺伝子を含むような長鎖DNAの判断に迷ったようである。単離されたDNAの化合物としての相違を認めながらも、Moore判事は化合物としての相違で判断せず、長鎖DNA配列の特許を禁止するかは米国議会の意思に委ねるという消極的な立場で賛成したといえる。Moore判事は、特許運用の変更がバイオ産業に与える影響を指摘した。
さらにMoore判事は、政府が提案した「マジックマイクロスコープ」テストに強く反対した。Moore判事は、このテストは子供じみていると非難し、過去の判例法と矛盾することも指摘した。
単離DNAクレームに関するBryson判事の意見
まず、Bryson判事はcDNAは実験室で作製されるものであり特許対象適格があると認めたが、DNA断片クレームの特許対象適格を否定した。このような主題は、化学標識（タグ）など、有用性に寄与する追加的な構造を記載している場合に特許するべきであると述べた。ただし、この議論のなかでBryson判事は、特許法101条や判例法についてほとんど検討していない。
Bryson判事は、長鎖DNAクレームの特許対象適格も否定した。Bryson判事は、自然状態から単離されてサイズが変化したというだけで特許可能とすることに疑問を呈している。地中からの鉱物の採掘や木から葉をもぎ取るのと同じアナロジーで、自然界にある状態と、単離された状態との間の構造上の相違はクレームの限定とはいえないと指摘した。換言すると、長鎖DNA配列はそれが自然状態にあるときと何ら機能が変わるものではないから、特許すべきではないとの立場である。最後にBryson判事は、遺伝子特許取得に関する米国特許庁の過去の運用の便宜を考慮すべきではないと述べ、運用の変更がバイオ産業に与える影響や米国議会の判断が必要であるかついてコメントしていない。
方法クレームに関する意見
3人の判事は、スクリーニング方法を除き、「分析」ないし「比較」するクレームはBilski判決のマシン－トランスフォーメーションテストの要件を満たさないとして特許対象適格がないとした。特にクレームには「比較」の工程だけがあり、その比較工程の応用（アプリケーション）までは記載されていないことを指摘した。またCAFCは「分析」や「比較」という文言は「抽出」や「配列決定」を意味するものではないと判断した。結局、CAFCは、方法クレームは「比較する」というメンタルな工程を記載しているに過ぎないとみなした。さらにCAFCは、DNAを抽出し配列を「決定」するす肯定はトランスフォーメーションがあると判断した他の判決との相違について触れた。CAFCは本件クレームには「決定」の工程が無いので、特許対象外であると結論した。ただし、単なる情報収集工程であるか否かは判断されず疑問が残る。
最薬物候補のスクリーニング方法についてCAFCは、特許対象外とした地裁の決定を棄却した。CAFCは、形質転換細胞の「増殖」はトランスフォームの工程であるとし、これは方法クレームの主題に入ると述べた。
Translated by Yoshiya Nakamura
Court of Appeals for the Federal Circuit, July 29, 2011
Lourie, Moore, Bryson
After nearly four months of consideration[1], the Court of Appeals for the Federal Circuit issued a decision in the controversial AMP v. USPTO case on Friday, July 29, 2011. Weighing in at just over a hundred pages total, the decision includes a majority opinion by Judge Lourie, a concurrence by Judge Moore and a dissent by Judge Bryson. The main point of contention between the three opinions relates to the patent-eligibility of the composition claims, particularly the claims which recite isolated long DNA sequences.
Standing
The first issue considered by the CAFC was whether the Plaintiffs had standing to sue. The Plaintiffs were a motley crew of doctors, patients, scientific organizations and advocacy groups. This wide breadth of Plaintiffs was one of the unusual aspects of this case. Some Plaintiffs, such as cancer patients, claimed standing based on the fact that they could not afford the costs of the genetic tests or obtain a second opinion, due to Myriad being the exclusive provider for this test in the United States. The Court quickly dismissed this reasoning, stating that “we fail to see how the inability to afford a patented invention could establish an invasion of a legally protected interest for purposes of standing.” Citing MedImmune, the Court succinctly stated: “[s]imply disagreeing with the existence of a patent or even suffering an attenuated, non-proximate, effect from the existence of a patent does not meet the Supreme Court’s requirement for an adverse legal controversy of sufficient immediacy and reality to warrant the issuance of a declaratory judgment.”
After disregarding those patients and organizations which had no direct contact with Myriad, the Court identified three Plaintiffs who required further analysis: Drs. Kazazian and Ganguly of the University of Pennsylvania, and Dr. Ostrer of New York University. Each of these doctors had received cease-and-desist letters in 1998 from Myriad telling them to stop providing commercial BRCA1/2 testing, with which they complied. However, the Court ruled that only Dr. Ostrer had standing in this case, because only he met the three requirements for standing outlined in Lujan v. Defenders of Wildlife: an injury in fact, a causal connection between the injury and the actions of Myriad, and that it be ‘likely’, not merely ‘speculative’, that a favorable decision will redress his injury. Drs. Kazazian and Ganguly stated that they would “consider” taking up BRCA gene testing if the claims were held invalid. On the other hand, Dr. Ostrer stated with certainty that he would “immediately begin” such testing if the claims were held invalid. The uncertainty of Drs. Kazazian and Ganguly resulted in their failing in the third element of Lujan, while Dr. Ostrer’s definite statement resulted in his having standing.
Myriad had also argued that the cease-and-desist letter, which was Myriad’s most recent communication with Dr. Ostrer, was over 10 years old and thus too stale to provide Dr. Ostrer with a reasonable apprehension of suit. The Court rejected this, by holding that even if the date on the calendar had changed since the last communications between Myriad and Dr. Ostrer, the positions of the parties had not. The technology remained largely the same, Myriad’s business remained largely the same, and Dr. Ostrer still wished to perform the BRCA tests. As such, the Court held that the time between the most recent communications and filing of the suit did not preclude Dr. Ostrer’s standing.
Finally, the Court discussed Myriad’s argument about redressability, which relates to the third prong of Lujan. In the reply brief and oral argument, Myriad argued that Dr. Ostrer should not have standing because even if the claims at issue were invalidated, his alleged injury would not be redressed. This is because his conducting the BRCA tests would also infringe other non-challenged claims, particularly those directed at probes and primers. The CAFC declined to comment on this point, because it did not wish to decide the “case within the case.” In other words, in order to bar standing based on this point, the Court would have to construe the non-challenged claims and determine whether or not infringement had occurred. The Court declined to do so.
In view of the above, the Court held that only Dr. Ostrer has standing. However, there is a recent twist. As of August 2011, Dr. Ostrer will move from his position at New York University School of Medicine, which offers genetic testing, to the Albert Einstein Medical Center, which “does not offer, and is not qualified to offer, clinical genetic testing.”[2] Myriad informed the CAFC of this in a letter, apparently sent shortly before the decision was issued. Since Dr. Ostrer will soon not be able to perform the BRCA tests, it seems that he may no longer have standing. It remains to be seen how this and any other future standing developments will affect the outcome of the case.
Composition Claims: Judge Lourie’s take
Moving to the merits, the majority reversed Judge Sweet’s decision that isolated DNA sequences are not patent eligible. Mostly relying on Chakrabarty, the Court stated that the distinction between a product of nature and something patent eligible under §101 “turns on a change in the claimed composition’s identity compared with what exists in nature.” The Court discusses the structural difference between isolated DNA and DNA in its natural form, such as cleaved bonds on the ends of the sequence and a difference in size between an isolated sequence and a whole chromosome.
The Plaintiffs had argued that because the isolated and native DNA contain the same genetic code, they are not “markedly different.” The Court disagreed by stating that this frames the patent eligibility question in the context of similarities, rather than differences. The Court states “the patent eligibility of an isolated DNA is not negated because it has similar informational properties to a different, more complex natural material that embodies it.” Judge Lourie’s reasoning extends to all types of isolated DNA: a long DNA sequence, a short DNA fragment, and cDNA.
Another unusual aspect of this case was the fact that the Department of Justice, represented by the Acting Solicitor General, filed an amicus brief and presented oral arguments. The government argued that the test of patent eligibility should be a “magic microscope”—if the exact sequence can be seen in nature, the sequence should not be patent eligible, but if the exact sequence cannot be seen present in nature, it should be patent eligible. Under this reasoning, cDNA, which lacks introns, would be patent eligible, since the sequence cannot be found in nature, but long DNA sequences and short DNA fragments found in nature would not be patent eligible. The majority argues that this point ignores the difference between science and invention. Judge Lourie states “[v]isualization does not cleave and isolate the particular DNA; that is the act of human invention.”
Finally, the majority briefly discusses the variety of colorful analogies made in this case: isolation of elemental lithium, extracting a diamond from the earth, removing a leaf from a tree, removing a kidney from a human, etc. However, majority comes back to a simple fact: isolated DNA “has a markedly different chemical nature from the native DNA.” The majority concludes that isolated DNA is therefore patent eligible subject matter. Additionally, the majority briefly notes that any decision to remove this subject matter from patent eligibility should be made by Congress.
Composition Claims: Judge Moore’s take
Next, I will skip over the majority’s discussion about the method claims, and discuss the concurrence and dissent, each of which addresses only the composition claims. Judge Moore reaches the same conclusion as Judge Lourie for each of the three types of compositions claims, but for a different reason.
First, Judge Moore discusses cDNA, which presents the easiest analysis, stating that cDNA is clearly patent eligible. She correctly identifies that fact that cDNA, which lacks introns, is not found anywhere in nature. Thus, it must be patent eligible. Using an interesting choice of words, Judge Moore “decline[s] to extend the law of nature exception to reach entirely manmade sequences of isolated DNA, even if those sequences are inspired by a natural template.”
Judge Moore then discusses DNA which is identical to that found in nature. She agrees with the majority, but for an additional reason beyond the difference in chemical structure. First, with respect to short DNA fragments, Judge Moore focuses on the “enlargement of the range of…utility,” citing Funk Brothers. She states that a short DNA fragment in its natural context cannot be used for diagnostic testing. Thus, she concludes that isolated DNA fragments do not “serve the ends of nature originally provided,” but rather lead to a “different and beneficial utility.”
As to lengthy DNA sequences including most or all of a gene, Judge Moore clearly struggles. Since these long sequences cannot be used for diagnostic testing, Judge Moore sees no “enlargement of the range of …utility.” Notably, Judge Moore states that if she were to decide this issue on a “blank canvas,” she may conclude that this type of claim was not patent eligible. Despite acknowledging a literal chemical difference, she appears to have difficulty with the lack of a new utility as compared with nature. Instead, Judge Moore gives deference to the lack of Congressional action barring lengthy DNA sequences.
The final section of Judge Moore’s concurrence includes a lengthy discussion of the possible impact of a change in policy on the biotechnology industry, and dissection of the positions of the government and dissent. Judge Moore notes the thirty year history of DNA patenting and the large biotechnology industry, stating that “leaving intact the settled expectations of property owners is particularly important in light of the large number of property rights involved, both to isolated DNA and to purified natural products generally.”
Judge Moore provides a strong rejection of the government’s “magic microscope” test, discussed above. She states that this test has “child-like simplicity” and requires that the magic microscope to also “make some decisions.” Furthermore, she states that this test would be inconsistent with previous case law. In particular, she identifies Funk Brothers, since under the “magic microscope” test, the subject matter of Funk Brothers would appear to be patent eligible. She also focuses on the negative impact of destroying the property rights of the large and innovative biotechnology industry, and echoes Judge Lourie’s feeling that any limits on isolated DNA claims should be by Congress.
Composition Claims: Judge Bryson’s take
Next, I discuss Judge Bryson’s dissent. As to cDNA claims, Judge Bryson agrees with Judges Lourie and Moore. Since cDNA must be created in a laboratory, and has a utility not found in nature, Judge Bryson regards cDNA as patent eligible.
As to short DNA fragments, Judge Bryson disagrees with Judges Lourie and Moore. Judge Bryson appears to be of the position that these fragments are not patent eligible, because they are too broad, and may be found throughout the genome. Moreover, Judge Bryson states that this subject matter should be claimed by reciting additional structure which confers utility, such as chemical tags. Judge Bryson provides little discussion regarding §101, or the relevant case law, when discussing short DNA fragments.
As to long DNA sequences, Judge Bryson also disagrees with Judges Lourie and Moore, for much of the same reason as why Judge Moore struggled with the issue. Judge Bryson discusses analogies such as extracting minerals from the earth and removing a leaf from a tree. Judge Bryson regards the majority opinion as an “oversimplification” and states that the “structural differences between the claimed “isolated genes” and the corresponding portion of the native genes are irrelevant to the claim limitations, to the functioning of the genes, and to their utility in their isolated form.” In other words, Judge Bryson seems to think that since lengthy sequences have no function other than that found in nature, they are not patent eligible.
Finally, Judge Bryson provides some comments about the history of gene patenting. Judge Bryson believes that USPTO’s previous practice should be afforded little weight, as was the case in Chakrabarty. Unlike Judge Moore, Judge Bryson provides no comments about the impact of a change in the law on the biotechnology industry. Unlike Judges Lourie and Moore, Judge Bryson provides no comment about deference to Congress on the question of patent eligibility of isolated DNA.
Method Claims
Moving back to the majority decision, all three Judges agreed on the outcome and reasoning for the method claims, all but one of which was deemed to recite non-patent eligible subject matter. Most of the method claims in question recited a method including the single step of “analyzing” or “comparing” a patient’s DNA sequence with a wildtype sequence. One method claim recited a method of screening for a potential drug, and included steps such as “growing” a transformed cell line, “determining” its growth, and “comparing” the growth to the wildtype.
As to the claims “analyzing” or “comparing” a patient’s DNA sequence with a wildtype sequence, the Court held that these claims did not comply with the machine-or-transformation test of Bilski. In particular, the Court stated that there is no application of this comparison, only the comparison itself. Although the claims recite that the sequence is “from a human sample” or “from said tumor,” the Court held that the claims do not recite steps of extracting DNA from a human sample or sequencing the extracted DNA. Myriad argued that the claims inherently required such extraction and sequencing, presumably because of the requirement that the sequence was “from a human sample” or “from said tumor.” However, the Court disagreed, and held that comparing and analyzing do not imply extracting or sequencing. Furthermore, the Court states that in the context of the specification, the term “sequence” refers broadly to the linear sequence of nucleotide bases.
In view of the above, the Court regards the method claims as reciting only a mental step of comparison. In other words, the claim would be infringed by a person looking at two pieces of paper, each having a DNA sequence printed on it, and mentally comparing the two. The Court briefly distinguishes over Prometheus v. Mayo, which will be heard by the Supreme Court later this year. The Court in Prometheus held that the “determining” step was transformative because it required manipulation of the sample. The Court notes the absence of a “determining” step in this case, which would apparently have been sufficient to include the subject matter of extracting the DNA and sequencing it. However, it is left as an open question whether, if recited, a step of “determining” the DNA sequence would be considered central to the claims or an insignificant data-gathering step.
Finally, the Court reverses the District Court’s holding regarding the method of screening for a potential drug. The Court notes the inherently transformative step of “growing” transformed cells, and states that this step is central to the claimed process. The Court also refutes the District Court’s assertion that this claim recites the scientific process itself. Since the claims recite a particular type of cell, it is an application of the scientific process, not the scientific process itself.
Conclusion
This decision should come as a relief to anyone in the biotechnology industry. Importantly, claims to isolated versions of natural products, not limited to DNA, remain patent eligible. Although Myriad lost on most of their method claims, they clearly won this battle. Their business model appears to be intact, at least due to the preservation of their composition claims, which are crucial for the practice of the diagnostic methods which form the cornerstone of their business.
The larger question surrounds method claims. I believe that the Court reached the correct decision here. However, the question of whether a “determining” step is in fact transformational remains controversial, and will be addressed in Prometheus. Furthermore, it remains unsettled whether “determining” a DNA sequence prior to comparison would be considered data-gathering, using the reasoning of In re Grams. Additionally, Applicants in similar cases should be mindful of drafting claims in such a way as to include transformational steps, but to avoid divided infringement issues.
It seems very unlikely that this is case will go away any time soon. It is likely that the Plaintiffs will either request an en banc hearing at the CAFC or petition the Supreme Court to hear the case. However, although Myriad is probably relatively satisfied with the outcome, they will likely challenge the standing issue again, particularly in view of the changing circumstances of the single party who was regarded as having standing.
Ryan Chirnomas is a Partner in the Biotechnology group at Westerman, Hattori, Daniels and Adrian LLP. Any questions or comments may be directed to rchirnomas@whda.com. This article is for informational purposes only. The comments herein are the views of the author only and do not necessarily represent the views of Westerman, Hattori, Daniels and Adrian LLP or its clients.
[1]Discussion of the Oral Hearing in this case can be found here: http://patentlawcenter.pli.edu/2011/04/05/ampvuspto/
