Obviousness or Inventive Step as Applied to Nucleic Acid Molecules: a Global Perspective

• Publication year: 2004
• Citation: Vol. 6 No. 2004

Amy Nelson⁰

I. Introduction

Obviousness, or inventive step, has been called the ultimate bar to patentability.¹ The purpose of the nonobviousness requirement is to complement the novelty requirement and to extend the scope of the relevant prior art beyond anticipatory prior art.² This ensures that an invention constitutes a sufficient advance in technology to warrant an exclusive right. Adoption of an obviousness standard is a balancing act that requires weighing the inventor's right to exclude and the public's need to gain useful technological knowledge in exchange for that patent right. As a consequence of its interpretive flexibility, the application of obviousness has varied greatly among nations. This is particularly true for its application to nucleic acid molecules.

The Agreement on Trade-Related Intellectual Property Rights ("TRIPS") has attempted to bring some international uniformity to the application of obviousness or inventive step rules.³ TRIPS Article 27(1) provides that "patents shall be available for any inventions, whether products or processes, in all fields of technology, provided they are new, involve an inventive step and are capable of industrial application."⁴ Exclusive patent rights are available for all products regardless of their status as an import or a domestic creation.⁵ The TRIPS Agreement has been ratified by 120 countries.⁶ TRIPS is an integral part of the WTO Agreement, and a country cannot be a member of the World Trade Organization ("WTO") without being a party to the TRIPS Agreement.⁷ As a signatory of TRIPS, the United States agreed to ensure that its obviousness requirement meets the standards of the 1994 Agreement.⁸ The European Patent Office's inventive step requirement is also governed by the TRIPS Agreement.⁹ Japan has both signed and ratified the TRIPS Agreement.¹⁰ Australia is also bound by the TRIPS Agreement.¹¹

TRIPS, however, only sets the minimum patentability standards with which signatories must comply.¹² National patentability rules may vary beyond the minimum, and member states are free to set their own intellectual property laws. To the extent that different countries have differing patentability standards, those differences in national laws may be significant. As a result, TRIPS allows for differing standards of inventive step or obviousness under different national laws.

In recent years, there has been an explosion of patent applications in biotechnology, particularly applications directed to nucleic acid molecules. TRIPS countries, however, have adopted a variety of standards for determining obviousness or inventive step for nucleic acid molecules. Part II discusses legal standards as applied in the United States, Australia, Europe, and Japan, with particular emphasis on the distinctions between U.S. laws and those of other countries. Part III discusses the implications of having different legal standards in different countries.

II. Standards for Determining Obviousness or Inventive Step of Nucleic Acid Molecules

A. United States

1. Statutory Law

Determination of obviousness in the United States is governed by Section 103 of the Patent Act of 1952, which recites that:

A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which such subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.¹³

2. Relevant Prior Art

In the United States, the prior art that is applied must be from an analogous field, and the number of references that are applied is not limited.¹⁴ The prior art that can be applied includes "secret art," i.e. pending patent applications.¹⁵ The prior art refers to everything that is known, published and available to the public in the past.¹⁶ Oral disclosures are only considered if they occurred within the boundaries of the United States.¹⁷ The United States provides a grace period that permits publication of the invention by the inventor up to one year prior to filing of the patent application.¹⁸

3. Prima Facie Test

Application of Section 103 was clarified in a seminal decision:

Under § 103, the scope and content of the prior art and the claims at issue are to be determined; differences between the prior art and the claims at issue are to be ascertained; and the level of ordinary skill in the pertinent art resolved. Against this background, the obviousness or nonobviousness of the subject matter is determined.¹⁹

One of the earliest court decisions regarding obviousness as it applies to nucleic acid molecules in the United States related to isolation of a human genomic DNA encoding erythropoietin ("EPO").²⁰ The prior art taught an isolated monkey cDNA encoding EPO.²¹ The United States Court of Appeals for the Federal Circuit (hereinafter Federal Circuit) held that while it might have been obvious to try to isolate the human genomic clone using the monkey cDNA as a probe, it was not obvious to succeed in isolating the human EPO gene.²² There was no reasonable expectation of success given the high degree of degeneracy of the probe that was required for ultimate success.²³ Hence, the court focused on the likelihood that the method of DNA isolation would succeed.

In stark contrast to the Amgen decision, more recent decisions by the Federal Circuit have focused on the structural obviousness of the nucleic acid molecules themselves, rather than on the obviousness of the methods for their isolation. In In re Bell,²⁴ the prior art disclosed amino acid sequences for insulin-like growth factor ("IGF") polypeptides, as well as general methods for cloning genes.²⁵ The court held that the claimed invention, directed to specific nucleic acid molecules that encode human IGF, was non-obvious because there are a vast number of nucleic acid molecules that could encode the prior art proteins, and the prior art failed to suggest which of the possible sequences was the human nucleic acid molecule.²⁶

The landmark decision In re Deuel²⁷ has set the stage for obviousness with respect to nucleic acids in recent years. The claimed invention was directed to an isolated nucleic acid molecule encoding heparin-binding growth factors ("HBGF"), proteins found in urine and placental tissue that stimulate cell division and replacement of damaged or diseased tissue.²⁸ The prior art disclosed the first 19 amino acids of heparin-binding brain mitogens ("HBBM"), proteins found in the brain that are identical for human and bovine, and the prior art also taught general methods of DNA isolation.²⁹ The Federal Circuit held that whereas structural relationships may provide the motivation to obtain new compounds by modifying prior art compounds, here, the prior art taught only proteins, not closely related DNA molecules.³⁰ In view of the degeneracy of the genetic code, and hence the multitude of DNA molecules that may encode any given protein, knowledge of the protein does not render obvious a particular DNA encoding it.³¹ Further, the Court clearly articulated that prior art methods for isolating DNA molecules are "irrelevant" to the obviousness test for DNA molecules thereby obtained.³²

The import of the decisions in Bell and in Deuel in the United States is that a DNA molecule will be determined to be obvious only if it is structurally similar to prior art products, even if one of skill in the art would consider it obvious to obtain the DNA molecule using familiar prior art methods. The Federal Circuit has focused on the obviousness of the nucleic acid sequence itself rather than on the obviousness of the method of isolating the nucleic acid sequence.³³ A DNA molecule is non-obvious and patentable because its sequence could not have been predicted without isolation and sequencing of the DNA molecule.³⁴ The prior disclosure of the amino acid sequence does not render the DNA sequence obvious due to the degeneracy of the genetic code.³⁵ Prior art methods for isolating and sequencing DNA are irrelevant.³⁶ As a consequence of the Federal Circuit decisions, the United States Patent and Trademark Office ("PTO") has a relatively low threshold for obviousness in the patenting of nucleic acid molecules as compared to most other countries.

Interestingly, after the Bell decision the Board of Patent Appeals and Interferences held that recombinant DNA molecules encoding swine growth hormone were obvious.³⁷ In Ex parte Movva, the prior art taught the partial amino acid sequence of swine growth hormone polypeptide, the high degree of sequence relatedness between swine, bovine and human growth hormone polypeptides, as well as isolated DNA molecules encoding human and bovine growth hormone.³⁸ The Board held that based on the prior art, it would have been obvious to one of ordinary skill in the art to isolate a DNA molecule encoding swine growth hormone using probes based on the partial amino acid sequence.³⁹ The Board distinguished the case from Bell because the record did not show that a large number of nucleic acids could encode the polypeptide as in Bell and because multiple DNA sequences encoding growth hormone polypeptides from different species were disclosed in the prior art unlike in Bell.⁴⁰

Shortly after the Deuel decision, the Board of Patent Appeals and Interferences held that a cDNA encoding brain beta-amyloid polypeptide associated with Alzheimer's disease was obvious.⁴¹ The prior art taught a polypeptide isolated from cerebrovascular amyloid deposits of Alzheimer's patients and provided guidelines for synthesis of degenerate oligonucleotide probes.⁴² The prior art also taught methods for constructing and screening cDNA libraries.⁴³ The Board held that it would have been obvious based on the prior art to isolate...