NEW YORK - In the present day of high-throughput sequencing, it's hard to remember that obtaining the sequence for a single cDNA could take days, months, even years. However, a great deal of currently patented biotechnology was born in that era.
When a nucleotide or amino acid sequence wasn't available, applicants often described nucleic acids or proteins, such as antibodies, by activity and a biological deposit in a recognized depository, such as ATCC. Applicants did not provide sequence information. In some instances, particularly in the case of antibodies, the practice continues to this day.
In its decision earlier this year in the case of Enzo Biochem v. Gen-Probe, a three-judge panel of the Federal Circuit, which hears all US patent litigation appeals, placed in doubt the validity of patents directed to DNA molecules in which a sequence was not provided but relied upon biological deposits to support the description of the DNA invention. This decision is known as Enzo I.
However, as a result of the patentee petitioning the Federal Circuit to rehear the case "en banc," or by all judges, the Enzo I panel vacated its earlier decision and sent the case back to the trial court for further hearing. This is called Enzo II.
The case centered on whether claims to nucleic acids in a patent held by Enzo Biochemical were properly described by a biological deposit of exemplary nucleic acids from the claimed groups, which included Gen-Probe, Chugai, Biomerieux, and Becton Dickinson. The specification of the patent referenced the deposits, but other than hybridization characteristics no sequences or structural description of any of the claimed nucleic acids were provided.
The first claim of the patent at issue in Enzo is directed to a nucleic acid that exhibits an at least five-fold preference in hybridization to N. gonorrhea over its close relative N. meningitides. The bacterial strains used to test hybridization preference were defined by reference to particular ATCC deposits. Hybridization conditions are also thoroughly described in the claim.
The fourth claim, which depends upon, and thus includes, everything in the first claim listed several such nucleic acids that preferentially hybridized to N. gonorrhea. The claim also covered mutated version of these nucleic acids that meet the hybridization and ratio requirements outlined in the first claim.
In Enzo I, the Federal Circuit addressed the issue of whether the biological deposit alone was sufficient to support the written description requirement. (This is a statutory requirement for patentability described in the Jan. 26, 2001, TrendSpotter column.)
In its barest form the written-description requirement simply means that the patent specification must include a description of the invention so that it is distinguishable as such. This is often equated with showing that the inventor was in possession of the claimed invention at least as a complete mental image.
However, the Enzo I panel found that even an invention that is "reduced to practice," or embodied in a physical form, may fail to meet the written description requirement if it is not described in sufficient detail in the patent specification.
The Enzo I court held that a reference to a biological deposit alone in a patent specification, without some more specific description of a nucleic acid embodied in the deposit, failed to provide a written description of the invention as required by law. Although a description of the claimed nucleic acids was provided (in terms of their ability to preferentially hybridize to the DNA of one type of bacteria as opposed to another related bacteria), their actual sequences or other physical data was not.
The Federal Circuit had previously decided in University of California v. Eli Lilly that a patent disclosing rat insulin cDNA did not provide a written description of human insulin cDNA even though it described functional characteristics of human insulin cDNA and actually enabled practitioners to make and use human cDNA.
The basis for the Lilly decision lay in the fact that no precise definition of the human genetic material, such as structure, formula, chemical name, or physical properties, was provided. The Enzo I court extended the Lilly decision to say that a reference to a biological deposit in the patent could not be used to provide a written description of the claimed DNA in the absence of a sequence or other physical characteristics.
Given the large number of patents in which a functional description of a nucleic acid or protein has been provided in the specification along with a reference to a biological deposit, the Enzo I decision called into question the value of a substantial basis of the biotechnology industry. For example, many, if not all, antibody claims characterize the antibody by what it binds and reference a deposit of the antibody. Enzo II reversed the decision in Enzo I.
The Enzo II court, for its part, addressed the usefulness of a biological deposit in providing a written description of an invention as well as other aspects of the written description requirement.
The decision is important for two reasons. First, it vacates Enzo I and thus restores value to a number of biotech patents whose validity was called into question by the earlier decision. Second, it provides an extensive commentary on the guidelines regarding the written description requirement issued by the US Patent and Trademark Office in January 2001. (For a description of this commentary, called the "Written Description Guidelines," you may read the April 20, 2001 TrendSpotter column.)
The Enzo II court held that a biological deposit coupled with a functional description of a claimed nucleic acid or protein meets the written description requirement if a known correlation exists between the described function and a deposited or described structure. Thus, if a claim to an "isolated antibody capable of binding to antigen X" combined with a deposit of the antibody should meet the written description requirement because there are well-defined structural characteristics for antibodies, the functional characteristics of antibody binding are well-known, and antibody technology is well developed.
More generally, so long as a biological deposit provides a well-defined type of molecule with known functional/structural correlations, a mere reference to the deposit coupled with a functional description may be sufficient to satisfy the written description requirement. This agrees with the assumptions and practice in the field of biotech patents for the past 10 to 20 years and supports the validity of most earlier biotech patents that relied upon biological deposits for description purposes.
This finding also is in accord with the Written Description Guidelines and cites them favorably. Other portions of the Guidelines are favorably referenced and discussed throughout the decision as well. At one point, the guidelines discuss the distinction between its utility to patent applications versus issued patents.
The favorable recognition of the Guidelines and discussion of the scope of their application is important for several reasons. The Guidelines themselves, unlike some other USPTO dictates, are not accorded the force of law; indeed, although they are given some deference in the courts, a decision contrary to a Guideline decision may be readily reached by a court. Therefore, until a court has commented on the Guidelines, or until other actions have been taken to given them the force of law, the legal correctness and proper applicability of the Guidelines is unclear.
However, until a specific portion of them is disagreed with by a court, the Guidelines will be applied to every patent application examined by the USPTO. Additionally, the acceptable way of applying Guidelines to those patents issued before the Guidelines are implemented are very uncertain until they are addressed by a court. This can result in the issuance of invalid patents or the denial of a patent for a patentable invention among other problems.
The court favorably commented on and borrowed several examples in the Guidelines, including the antibody example above. The court also examined several examples in the Guidelines addressing hybridization and nucleic acids, in particular. It agreed that if some deposits are provided and strict hybridization requirements are included in a patent claim, the claim may be valid not only for the deposited nucleic acids, but also for similar ones meeting the strict hybridization requirements.
Moreover, the Enzo II Court also noted that the USPTO has promulgated rules for Deposit of Biological Materials, which are required for biological material that cannot be described or enabled in words.
Now that portions of the Written Description Guidelines have been addressed by the Federal Circuit, their status as an appropriate framework for pending patent applications has the imprimatur of the Court. Further guidance regarding their applicability to issued patents is also provided in Enzo II. Although a US patent is always presumed valid, this presumption may be overcome in court. Any patent is less likely to be found invalid by a court if it is examined using guidelines recognized by the Court as an appropriate framework. Additionally, patentable inventions are less likely to be denied patents when correct guidelines are implemented.
Overall, the Enzo II decision helps the biotechnology industry in two ways. It affirms the long-held assumption that a biological deposit may be used to help satisfy the written description requirement. It also provides favorable commentary and discussion of the Written Description Guidelines. These two factors support the continued validity under the written description requirement of both currently issued patents and those to be issued in the future.
Rochelle K. Seide is a partner at the law firm of Baker Botts. She is experienced in biotechnology, intellectual property, and patent issues, and also has a Ph.D. in human genetics. Michelle LeCointe is an associate at Baker Botts and a registered patent agent. They can be reached at[email protected] and [email protected]